bluuebunny/crossref_metadata_2025 huggingface dataset:
The blockade of serotonin uptake into synaptosomes: relationship to an interaction with monoamine oxidase inhibitors
Authors: Sinclair John G. , Lo Grace F.
Published: April 2011

To test the hypothesis that the hyperpyrexia produced by meperidine and detromethorphan in rabbits pretreated with a monoamine oxidase inhibitor is related to inhibition of neuronal uptake of serotonin (5-hydroxytryptamine (5-HT)), fluoxetine (Lilly 110140) was studied. This potent and specific 5-HT neuronal uptake blocker was administered to phenelzine-pretreated rabbits and found to produce a lethal hyperpyrexia in doses equal to or greater than 2.5 mg/kg. The order of potency in blocking 5-[14C]HT uptake into synaptosomes prepared from rabbits was: fluoxetine > meperidine = dextromethorphan = levorphanol > anileridine > alphaprodine > morphine. Since fluoxetine, meperidine, and dextromethorphan produce hyperpyrexia in phenelzine-pretreated rabbits, whereas anileridine, alphaprodine, and morphine do not, there appears to be some correlation between the hyperpyrexic response and inhibition of 5-HT uptake. The exception is levorphanol, which is not hyperpyrexic despite being equipotent with meperidine and dextromethorphan in inhibiting 5-HT uptake. The ineffectiveness of levorphanol in producing hyperpyrexia may be due to its marked depressant properties, since the addition of another depressant drug (pentobarbital) antagonized the hyperpyrexic effect of meperidine.
Effect of reserpine on the structure–activity relationships for the inhibition of noradrenaline uptake in adrenergic nerves in rat and rabbit ventricle by phenethylamines
Authors: Paton D. M. , Golko D. S.
Published: April 2011

Ventricular tissue from the hearts of normal and reserpine-pretreated rats and rabbits were exposed to pargyline, tropolone, and hydrocortisone to inhibit monoamine oxidase (EC 1.4.3.4), catechol-O-methyltransferase (EC 2.1.1.6), and extraneuronal uptake, respectively. To examine the structure–activity relationships for inhibition of noradrenaline uptake, the inhibition of the 10-min uptake of (−)-[3H]noradrenaline by sympathomimetic amines was determined and ID50 values calculated. In reserpine-pretreated tissues, the most potent inhibitory agents studied were amines lacking phenolic hydroxyl groups (i.e., β-phenethylamine, (+)- and (−)-amphetamine). Addition of one or two phenolic hydroxyl groups, a β-hydroxyl group, or an N-methyl group generally decreased inhibitory potency, while α-methylation had little effect. Amines with large N-substitution and phenolic O-methyl groups were the least potent inhibitory agents. The stereoisomers of amphetamine, noradrenaline, and metaraminol did not differ in potency. However, the stereoisomers of ephedrine did, the order of potency being (−)-ephedrine > (±)-ephedrine > (+)-ψ-ephedrine > (−)-ψ-ephedrine. These structure–activity relationships are the same as those previously found for the acceleration of efflux of extragranular noradrenaline. Amines also released (−)-[3H]noradrenaline from reserpine-pretreated tissues. Results obtained using ventricles from nonreserpinized rats and rabbits showed two important differences. Firstly, sympathomimetic amines were much less potent releasers of (−)-[3H]noradrenaline from such tissues. Secondly, amines lacking phenolic hydroxyl groups were, on the average, five- to seven-fold less potent as inhibitors of (−)-[3H]-noradrenaline uptake. However, the inhibitory potencies of phenolethylamines and catecholamines were generally similar to those found in reserpine-pretreated tissues. These studies have demonstrated that reserpine pretreatment potentiates the inhibitory potency of phenethylamines and phenylethanolamines.
Effects of estrogen and progesterone on pulsatile discharges of luteinizing hormone in the ovariectomized rat
Authors: Weick Richard F.
Published: April 2011

The effects of both acute and chronic systemic administration of estrogen and progesterone on pulsatile discharges of luteinizing hormone were observed in ovariectomized rats. Intravenous injection of 10 μg of 17β-estradiol resulted in a gradual decrease in plasma luteinizing hormone (LH) concentrations but did not completely block the pulsatile discharges. Subcutaneous implantation of Silastic capsules containing 17β-estradiol caused similar decreases; plasma LH concentrations decreased for the first 6 h but periodic increases continued, with nearly complete suppression of such pulsatile discharges by 24 h. Such inhibition was maintained for the 14-day course of the experiments. Progesterone alone, whether administered by Silastic capsule or by daily subcutaneous injection in oil, was without apparent effect on either plasma LH concentrations or temporal patterns of the hormone. Further, progesterone combined with 17β-estradiol was little, if any, more effective in this regard than estradiol alone. These results indicate that estrogen is an effective feedback signal inhibiting pulsatile release of LH in the rat and that progesterone alone has little, if any, influence in this regard.
Oxygen-tension-dependent pulmonary vascular responses to vasoactive agents
Authors: Tucker Alan , Weir E. Kenneth , Grover Robert F. , Reeves John T.
Published: April 2011

There have been recent indications that oxygen may nonspecirically oppose pulmonary vasoconstriction induced by a few vasoactive agents. Therefore, we examined the effect of four inspired oxygen tensions on the pulmonary vascular responses to exogenous prostaglandin F2α (PGF2α), serotonin (5-HT), 2-methylhistamine (2-MeH) (an H1-receptor agonist), histamine (after H2-receptor blockade with metiamide), and prostaglandin E1 (PGE1) in anesthetized dogs. An oxygen tension dependency on the pulmonary vascular responses to these vasoactive agents was observed, with each agent exhibiting maximal responses at different ranges of oxygen tension. PGF2α and PGE1 were most effective during hypoxia, while 5-HT, histamine, and 2-MeH produced maximal responses during normoxia. A comparison of dose–response curves for PGF2α during breathing of two inspired oxygen tensions indicated a decreased sensitivity, but not decreased reactivity, with the higher oxygen tension. The action of variable oxygen tensions on pulmonary vascular responsiveness to vasoactive agents suggests another role for oxygen in the control of the pulmonary circulation. It is not clear if oxygen acts non-specifically on the vascular smooth muscle, or if it alters the metabolic mechanisms of vasoactive agent action.
Cyclic AMP and the positive inotropic effect of norepinephrine and phenylephrine
Authors: Martinez T. T. , McNeill J. H.
Published: April 2011

Time-response studies of the effects of norepinephrine and phenylephrine revealed that both agonists caused an increase in cyclic AMP levels before increases in contractile force in either the electrically stimulated left atria or spontaneously beating right atria of the rat. Norepinephrine caused a nearly sixfold increase in cyclic AMP, whereas phenylephrine produced only a 50% increase in the nucleotide. Pretreatment with reserpine did not affect the norepinephrine cyclic AMP response; however, the phenylephrine cyclic AMP response was abolished. Reserpine pretreatment did not significantly affect the contractile responses of either amine. In the presence of propranolol, norepinephrine was found to have the ability to produce an increase in contractile force in which cyclic AMP was apparently not involved. The time course of the contractile response induced by adrenergic amines was found to be remarkably influenced by the chronotropic response in spontaneously beating preparations while the cyclic AMP response was not greatly affected. This difference in the contractile response may be due to the ability of the chronotropic response to influence the flux of calcium through the cell membrane.
Effects of acetylcholine on potassium-induced changes of GABA and taurine uptakes and release in cerebral cortex slices from the rat
Authors: Benjamin A. M. , Quastel J. H.
Published: April 2011

Acetylcholine, in presence of eserine, has little or no effect on the potassium-ion-suppressed concentrative uptakes of GABA and taurine by rat brain cortex slices in contrast with its effect on those of L-glutamate, L-aspartate, and glycine. Potassium ions at a concentration of 30 μequiv./ml in the incubation medium has a marked suppressive effect on the uptakes of GABA and taurine when there is no apparent change in the sodium ion content of the brain tissue. It is concluded that some factor, besides the change in sodium gradient, operates in the mechanism of potassium suppression of GABA and taurine uptakes. Acetylcholine diminishes the potassium-evoked release of endogenous GABA and taurine from brain slices. Its action is Ca2+ dependent and is diminished by atropine. Acetylcholine does not affect the potassium-accelerated release of GABA from brain slices previously loaded with this amino acid. The differences in uptake and release phenomena exhibited by GABA and taurine from those of L-glutamate and L-aspartate may be due to differences between the mechanisms, as well as the sites, of cerebral uptake and release of these two groups of amino acids.
Species variation with respect to the metabolism and excretion of d-amphetamine and d,l-N-hydroxyamphetamine succinate
Authors: Danielson Terry J. , Davis Bruce A. , Boulton Alan A.
Published: April 2011

The metabolism of amphetamine and N-hydroxyamphetamine was studied in the rat and mouse. Extensive reduction of N-hydroxyampnetamine to amphetamine occurred in both species. In addition, para-hydroxylation of amphetamine was a common metabolic route, although it was more predominant in the rat. No appreciable difference in the 24-h excretion of amphetamine and p-hydroxyamphetamine in either species was seen after substitution of N-hydroxyamphetamine for amphetamine.
The role of coronary flow and pressure as determinants of myocardial oxygen consumption in the presence or absence of vasomotor tone
Authors: Zborowska-Sluis D. T. , Mildenberger R. R. , Klassen G. A.
Published: April 2011

When coronary flow was kept constant and coronary pressure increased by angiotensin or decreased by dipyridamole, myocardial oxygen consumption (MVO2) remained unchanged. When vasomotor tone was abolished by dipyridamole or was intact, changing coronary flow resulted in a change in MVO2 in the same direction as flow; this change in MVO2 was in part the result of a significant alteration in coronary oxygen extraction. These results suggest that coronary flow, but not coronary pressure is an important determinant of MVO2 both in the presence or absence of vasomotor tone.
The relationship between oxygen extraction and extravascular mean transit time in the canine heart
Authors: Mildenberger R. R. , L'Abbate A. , Zborowska-Sluis D. T. , Klassen G. A.
Published: April 2011

A significant relationship was observed between myocardial oxygen extraction and the extravascular mean time transit time. This relationship implies that oxygen extraction by the myocardium is a time-dependent process, and emphasizes the critical link between blood flow and myocardial oxygen consumption.
Effects of thyroid hormones and cold exposure on turnover of norepinephrine in cardiac and skeletal muscle
Authors: Tedesco Joseph L. , Flattery K. V. , Sellers E. A.
Published: April 2011

[3H]Norepinephrine ([3H]NE) was injected intravenously to euthyroid, hypothyroid, and hyperthyroid rats kept at 23 °C, acutely exposed to 4 °C and acclimated to 4 °C. The decline of specific activity in heart muscle (taken as an index of turnover) was measured at 10 min and [Formula: see text], 6, 12, and 18 h after injection. Turnover was significantly higher in each treatment group at 4 °C than at 23 °C. At 23 °C turnover in the hypothyroid group was higher than in the euthyroid, which in turn was higher than in the hyperthyroid group (half times 5, 8.3, and 10.8 h respectively (P < 0.001). After 12 h at 4 °C, the same relationship was found (half times 1.9, 3.5, and 4.3 h respectively (P < 0.001). After acclimation to 4 °C, turnover in the hypothyroid group was higher than in the euthyroid or hyperthyroid groups (P < 0.001) with half times of 2.1, 4.1, and 3.9 h. These values were not significantly different from those of the same treatment groups acutely exposed to 4 °C. The highest turnover rates were in rats with lowest serum thyroxine (T4). Nevertheless hyperthyroid rats exposed to 4 °C had increased turnover rates in spite of high serum T4 concentration. The decline in specific activity of [3H]NE is attributable to 'dilution' by newly synthesized NE and hence it is unlikely that the effect of T4 was produced by inhibition of biosynthesis. Decline of specific activity of [3H]NE in gastrocnemius–soleus muscle of euthyroid rats was measured at 10 min and 6 and 12 h after injection. Half times for animals at 23 °C, 4 °C, and acclimated to 4 °C were 35, 19, and 17 h. The latter two values (as with heart) did not differ significantly. The findings afford direct evidence that increased synthesis and secretion of NE occur in rats exposed to 4 °C and a partial reciprocal relationship exists between thyroid hormonal activity and turnover of NE.
Endocrine effects of the pineal gland and neutralization of circulating melatonin and N-acetylserotonin
Authors: Niles L. P. , Brown G. M. , Grota L. J.
Published: April 2011

Adrenocortical function was studied in rats after shampinealectomy, pinealectomy, or immunization against melatonin and N-acetylserotonin (NAS). Pineals were stimulated to increase melatonin synthesis by blinding or exposure to 23 h of darkness daily. Blinding elevated morning corticosterone levels without altering the corticosterone response to novelty stimulation. Among blinded animals, pinealectomy partially reversed and immunization completely reversed the elevations in morning steroid levels. Exposure to short daily photoperiods flattened the diurnal corticosterone rhythm. Pinealectomy did not affect morning corticosterone levels but reduced evening corticosterone levels. More importantly, immunization resulted in reduced corticosterone levels throughout the diurnal cycle. These findings suggest that melatonin and (or) NAS may be involved in the regulation of resting diurnal adrenocortical function.
Blood and plasma volume changes in dogs after sympathectomy with 6-hydroxydopamine
Authors: Porlier Gerald A. , Nadeau Reginald A. , Champlain Jacques de
Published: April 2011

The effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) on blood volume was studied in unanesthetized splenectomized and nonsplenectomized dogs. A significant increase in total blood volume essentially accounted for by a marked plasma volume expansion was found in both groups after 6-OHDA treatment (50 mg/kg). The red cell volume in the nonsplenectomized dogs was significantly reduced 3 and 7 days after sympathectomy but returned to normal after 15 days. In contrast, the red cell volume was unchanged in the splenectomized dogs after sympathectomy. The blood volume changes were accompanied in both groups by significant decreases in hematocrit in plasma sodium and potassium and in serum protein concentrations while serum calcium concentrations were only slightly increased. These results confirm that the inhibition of adrenergic tone directly influences blood volume. They also indicate that an increase in blood volume constitutes an important compensatory mechanism for the long-term maintenance of adequate blood pressure levels after chemical sympathectomy by 6-OHDA.
Response of oculomotor neurons to eye muscle stretch
Authors: Tomlinson R. D. , Schwarz D. W. F.
Published: April 2011

Neurons within the ventral portion of the oculomotor nucleus respond to stretch of extraocular muscles. Response latencies range from 30 to 170 ms. Antidromically identified extraocular motoneurons with this input have slowly conducting axons in the range of 30 to 50 m/s. Only responses to stretch of muscles other than those innervated by these motoneurons were recorded. Responses to stretch of several muscles from both eyes are common.
Measurement of blood oxygen saturation using a multichannel fiberoptic oximeter–densitometer
Authors: Sekelj P. , Retfalvi S. , Lavoie A.
Published: April 2011

Design principles and performance of a new fiberoptic oximeter–densitometer for measurement of blood oxygen saturation are described. This instrument is capable of performing measurements using either an intravascular catheter, flow-through cuvette, or earpiece. The operations of the flow-through cuvette and earpiece are based on the principles of light transmission, that of the catheter on the principles of hemoreflection. The system incorporates five interference filters permitting the selection of a particular wavelength or combination of wavelengths to perform different modes of operation. Estimates using both catheter and cuvette appeared to be independent of variations over a wide range in hematocrit and flow rate. In the range from 20 to 100% saturation the standard deviation of the differences between the in vitro estimates by the catheter and (or) cuvette and the Van Slyke analyses were 1.62 and 1.73%, respectively. In 53 children with congenital heart disease (22 cyanotic) values calculated from readings by the earpiece were related to values of arterial oxygen saturation as measured by American Optical Company reflection oximeter at the time of cardiac catheterization. In the range from 50 to 100% saturation, the regression line between the two techniques was linear and the standard deviation of the differences was 2.89% (3.12% in cyanotic children alone).The method provides a high degree of compensation for variations in skin pigmentation.
Rat intestinal and renal calcium-binding proteins
Authors: Harrison J. E. , Hitchman A. J. W. , Gordon G. B. , Hasany S. A.
Published: April 2011

The effect of vitamin D activity on the major renal Ca-binding protein has been compared with that on the intestinal Ca-binding protein. Using a method based on Ca-binding capacity, these proteins were measured in vitamin D deficient rats after vitamin D treatment for varying periods up to 5 days. Since P deficiency has been shown to stimulate synthesis of the active metabolite 1,25-dihydroxycholecalciferol, a similar experiment was done on rats fed a P-deficient diet for periods up to 21 days. The renal Ca-binding protein was unchanged by vitamin D treatment to vitamin D deficient rats and was only slightly increased (50%) by phosphate deficiency. By comparison, the intestinal protein was increased twofold by vitamin D treatment and fivefold by phosphate deficiency. Results indicate that vitamin D activity has no direct effect on the major renal Ca-binding protein.
Discrete-trial control of morphine self-injection behaviour in squirrel monkeys: effects of naloxone, morphine, and chlorpromazine
Authors: Stretch Roger
Published: April 2011

Intravenous morphine self-injection behaviour was studied using a new discrete-trials procedure in monkeys. Morphine self-injection was most probable when small unit doses (10–100 μg/kg per injection) were available and least frequent, even in comparison with saline substitution, at doses of 300 and 400 μg/kg per injection. Despite variation of the inter-trial interval from 50 to 300 s small injection doses (25 and 100 μg/kg per injection) continued to sustain more frequent self-injection responding than a larger unit dose (400 μg/kg per injection). When daily sessions consisted of 40 trials at an inter-trial interval of 50 s, morphine self-injection behaviour (100 μg/kg per injection) was neither increased nor consistently decreased by naloxone pretreatment (0.1–1.0 mg/kg im). In subsequent experiments, daily sessions consisted of two sets of 40 discrete trials, separated by a time-out (TO) period. When monkeys were pretreated with morphine (5.6 mg/kg im) before a given session, responding for drug injections was suppressed; the effect was reversed by naloxone (1 mg/kg im) which, if injected at TO, reinstated morphine self-administration behaviour. When an injection of chlorpromazine (5.6 mg/kg im) preceded a given session, responding for morphine injections was also suppressed; naloxone (1 mg/kg im) failed to reinstate chlorpromazine-suppressed responding, indicating that naloxone acted as an acute morphine antagonist under some circumstances, but did not otherwise influence behaviour. When the unit dose of morphine was increased to 200 μg/kg per injection, naloxone (1–3 mg/kg im) elicited agitation and occasional vomiting in each monkey tested, but did not suppress their drug-taking behaviour. Though small increases in morphine intake were observed after naloxone pretreatment, substantial increases in response output during the inter-trial interval, with a consequent loss of stimulus control normally exerted by the trial signal, were observed. These results were interpreted in terms of acute, antagonist-precipitated withdrawal signs, not evident in response to naloxone pretreatment when drug self-injection responding was maintained on a daily basis by a limited number of smaller unit injection doses of morphine (50 or 100 μg/kg per injection).
Biochemical reactions involved in pancreatic enzyme secretion. 2. Inhibitory effects of tetracaine and atropine
Authors: Morisset J. , Beaudoin A. R.
Published: April 2011

Pancreatic enzyme secretion induced by urecholine or cholecystokinin–pancreozymin (CCK–PZ) is inhibited by tetracaine. If the pancreatic tissue is preincubated with tetracaine then washed out, the subsequent response to CCK–PZ is not affected while that to urecholine is impaired. In contrast with atropine, tetracaine loses its inhibitory potency once secretion has been initiated by urecholine before the addition of the local anaesthetic. Calcium efflux studies have shown that addition of tetracaine in vitro is associated with release of calcium in the incubation medium. This effect on calcium efflux might explain partly the inhibitory action of the drug.
Biochemical reactions involved in pancreatic enzyme secretion. 4. Effects of cytochalasin B on functions of the exocrine pancreas
Authors: Morisset J. , Beaudoin A. R.
Published: April 2011

These experiments were performed to evaluate the effects of cytochalasin B on pancreatic enzyme secretion and thus perhaps establish a role for microfilaments in the exocytosis process. The alkaloid at a concentration of 1 μg/ml (2 μM) inhibits amylase secretion induced by urecholine or cholecystokinin-pancreozymin (CCK-PZ) but does not modify that induced by dibutyryl cyclic AMP. The inhibitory effect of the drug is reversible after a 30-min washing out period. It does not affect O2 consumption, basal calcium efflux, or efflux caused by CCK-PZ. Amino acid accumulation in the tissue and their incorporation into proteins are not modified. It is suggested that cytochalasin B inhibits pancreatic enzyme secretion, probably through an effect on the microfilament system.
Urinary cyclic AMP excretion during volume expansion in the rat
Authors: Nawar Tewfik
Published: April 2011

We have studied the effect of volume expansion with 0.9% saline solution (10% body weight in 1 h) on urinary cyclic AMP excretion in rats.In nine normal rats urinary cyclic AMP excretion (picomoles/minute) was 113.9 ± 9.9 during the control period, rose significantly to 171 ± 20 during the first 10 min of expansion, came back to control levels for the next 20 min, and finally decreased significantly to 48.8 ± 13.2 at the end of the expansion period. In nine parathyroidectomized rats control cyclic AMP excretion was 78.0 ± 4.5, did not rise during expansion, and decreased significantly (to 33.7 ± 4.1) at the end of the expansion period.The transient increase in cyclic AMP excretion observed in normal rats could be due to parathyroid hormone release. Our studies do not allow us to explain the subsequent decrease noted in both groups.
Effect of ethanol tolerance on release of acetylcholine and norepinephrine by rat cerebral cortex slices
Authors: Clark J. W. , Kalant H. , Carmichael F. J.
Published: April 2011

The release of acetylcholine (ACh) by rat cerebral cortex slices, with and without electrical stimulation, and the effect of ethanol (EtOH) on this release were examined during the acquisition and loss of EtOH tolerance in vivo. ACh was measured by pyrolytic monodemethylation and gas–liquid chromatography. Electrical stimulation of control slices in medium containing diisopropyl phosphofluoridate (1.26 μM) and atropine (0.3 μM) increased ACh release by 88 ± 12%. Addition of 0.11 M EtOH to the medium had negligible effect on ACh release from unstimulated slices, but reduced the effect of stimulation to 51 ± 10%. After chronic treatment with EtOH by gavage or in a liquid diet, rats became tolerant to EtOH in vivo as shown by reduced impairment on the moving belt test. Slices from tolerant rats showed increased release of ACh in response to electrical stimulation and less inhibition of this response by added EtOH. The changes had disappeared by 2 weeks after cessation of EtOH treatment.Similar findings were obtained by measurement of release of [14C]ACh from slices preloaded with [14C]choline, except that electrical stimulation in the absence of EtOH appeared to cause a smaller increase in slices from chronic EtOH animals than from controls. This may reflect differences in isotope dilution. Release of [3H]norepinephrine was less affected by EtOH than that of ACh. The findings suggest that tolerance to EtOH is accompanied by increased ACh release by cortical neurones, as well as decreased direct inhibitory effect of EtOH on this, but do not permit any conclusion about the relative importance of such changes in various parts of the brain.
Discrete-trial control of cocaine self-injection behaviour in squirrel monkeys: effects of morphine, naloxone, and chlorpromazine
Authors: Stretch Roger
Published: April 2011

Intravenous cocaine self-injection behaviour was studied using a new discrete-trials procedure in monkeys. Daily sessions consisted of two sets of 40 discrete trials, separated by a 5-min time out (TO) period; the intertrial interval during each segment of the session was equal to 50 s. In the first experiment, cocaine self-injection behaviour (15 μg/kg per injection) was suppressed in a dose-dependent manner by morphine pretreatment (1–5.6 mg/kg, im). When cocaine self-injection responding was suppressed by morphine pretreatment (3 or 5.6 mg/kg, im), the morphine antagonist, naloxone (0.01–1.0 mg/kg, im), reinstated drug-taking behaviour; the effect depended upon the dose of the antagonist and upon the amount of morphine given to suppress cocaine self-administration behaviour. When monkeys were pretreated with chlorpromazine (0.03–5.6 mg/kg, im) before a cocaine self-injection session, small doses marginally increased responding and larger doses exerted a suppressive effect. These effects were observed when cocaine was available at a unit dose of 15 μg/kg per injection. When the unit dose of cocaine was increased to 300 μg/kg per injection, small doses of chlorpromazine (0.03–1 mg/kg, im) exerted no clearly detectable effects, though responding for drug injections was profoundly suppressed when sessions were preceded by chlorpromazine pretreatment at doses of 3 and 5.6 mg/kg, im. In this experiment, drug intake per session was greater when a large injection dose (300 μg/kg per injection) was available for self-administration than when a small dose (15 μg/kg per injection) could be self-injected; the frequency of drug self-injection was reduced, however, when the larger unit dose of cocaine replaced the smaller one. When considered in relation to the results of other experiments, it is evident that control of cocaine self-injection responding by a discrete-trials procedure results in schedule-dependent behaviours that differ in relative sensitivity to drug pretreatments from cocaine-reinforced responding controlled by fixed-ratio schedules of drug reinforcement.
Proximal–distal absorptive gradients in the in vivo intestine of normal and infected (Hymenolepis diminuta: Cestoda) rats
Authors: Podesta R. B. , Mettrick D. F.
Published: April 2011

Using a single-pass perfusion technique, H2O, Na+, Cl−, HCO3−, and glucose absorption were studied in the jejunum and proximal and distal ileum of rats either uninfected or infected with a tapeworm parasite (Hymenolepis diminuta). The effect of parasitization, region of the intestine, type of buffer, and concentration of glucose in the perfusion fluids on the transport data were analyzed by univariate and multivariate techniques.Proximal–distal flux gradients were observed for water and all the solute species studied, as well as for glucose- and bicarbonate-stimulated salt and water transport; there was a decreasing sensitivity to low pH proceeding distally. The major regional differences occurred between the proximal and distal ileum, with the fluxes in the jejunum being similar to those in the proximal ileum. Na+, H2O, and glucose transport decreased, while Cl− absorption increased, proceeding distally.The parasites diminished the rates of absorption of glucose, salt, and water, and altered the flux gradients, particularly the Na+ and HCO3− transport gradients. The differences in the gradients between control and infected animals were related to differential sensitivity of the different transport systems in the various regions of the gut to parasitism.
Influence of cold exposure and thyroid hormones on regulation of adrenal catecholamines
Authors: Roy M. L. , Sellers E. M. , Flattery K. V. , Sellers E. A.
Published: April 2011

Since thyroid hormones influence urinary excretion of catecholamines after exposure to cold, the effects of hyper- and hypo-thyroidism on adrenal tyrosine hydroxylase (TH) (EC 1.14.16.2), phenylethanolamine-N-methyl transferase (PNMT) (EC 2.1.1.28), and serum dopamine-β-hydroxylase (DβH) (EC 1.14.17.1) of rats at 23 and 4 °C were studied. TH changes resembled the urinary excretion pattern at 4 °C in being higher after 8 days than after 1 day of exposure, and in declining as acclimation occurred. At 23 °C, TH activity of hypothyroid rats was significantly higher than in euthyroid or hyperthyroid animals, and after 1 day at 4 °C the value increased even more. While in the hypothyroid animals at 4 °C the concentration of adrenal catecholamines was less, the epinephrine to norepinephrine ratio was higher than at 23 °C. Very high TH activity with a decline in catecholamine concentration suggests that the capacity of TH had been exceeded. PNMT activity was significantly elevated in this group. TH activity was not decreased in the hyperthyroid group at 23 °C, and was increased after 8 days at 4 °C, suggesting that circulating thyroid hormones have no direct inhibitory effect on TH. Serum DβH was elevated after exposure to 4 °C, regardless of thyroid hormonal status. The activation of adrenal TH in hypothyroid rats at 23 °C and of TH, PNMT, and serum DβH at 4 °C is probably the result of increased activity of the sympathetic nervous system.
Calcium-linked changes in myocardial metabolism in the isolated perfused rat heart
Authors: Dhalla N. S. , Yates J. C. , Proveda V.
Published: April 2011

Rat hearts were perfused for 40 min with aerobic medium containing different concentrations of calcium (0–5 mM) and their abilities to take up and oxidize glucose, and to produce lactate and glycerol were examined in addition to measuring glycogen, lipids, cyclic AMP, and high energy phosphate stores. Increasing the concentration of calcium was found to decrease myocardial glycogen but increase glucose uptake, glucose oxidation, and lactate release. A decrease in myocardial triglycerides and an increase in free fatty acid contents as well as glycerol release without any changes in cholesterol and phospholipid contents were observed upon increasing the concentration of external calcium. In comparison with the hearts perfused with Ca2+-free medium, the levels of creatine phosphate and ATP were lower and that of ADP higher in hearts perfused with medium containing 5 mM calcium. No differences in AMP and cyclic AMP contents were seen among hearts perfused with different concentrations of calcium. The contractile activity initially increased upon increasing the concentration of calcium from 1.25 to 5 mM and then declined towards the control level. The hearts were unable to generate contractile force in the absence of calcium, whereas the contractile force decreased and then began to recover upon perfusing the hearts with 0.31 mM calcium. These results indicate that elevated levels of intracellular calcium stimulate glycogenolytic, glycolytic, and lipolytic processes in myocardium directly.
Effect of p-chlorophenylalanine on development of cross-tolerance between pentobarbital and ethanol
Authors: Frankel D. , Khanna J. M. , LeBlanc A. E. , Kalant H.
Published: April 2011

Rats developed cross-tolerance to the motor-impairing effects of ethanol after daily oral administration of pentobarbital. Chronic administration of p-chlorophenylalanine (p-CPA), in a dosage regimen previously demonstrated to maintain extensive brain serotonin (5-HT) depletion, slowed down cross-tolerance development. p-CPA did not appear to exert this effect by altering the disposition of ethanol, since blood ethanol levels measured 20 min after ethanol administration were not affected by p-CPA treatment. This study extends our previous findings with respect to the inhibitory effects of p-CPA on tolerance development to ethanol and pentobarbital, and suggests that 5-HT may play a role in cross-tolerance development between ethanol and pentobarbital.
Responses to electrical stimulation, noradrenaline, serotonin, and vasopressin in the isolated ear artery of the developing lamb and ewe
Authors: Wyse D. G. , Petten G. R. Van , Harris W. H.
Published: April 2011

Responses of isolated helical strips of ovine ear artery to electrical stimulation of postganglionic adrenergic neurons and exogenous agonists were studied at various stages of development from 110 days of gestation through to adulthood. Only rudimentary responses were observed at 110–115 days of gestation. A parallel development of responses to noradrenaline (NA), serotonin, and lysine vasopressin began sometime after 110–115 days of gestation and continued until 133–137 days of gestation but there was little development of the latter responses until more than 3–5 days post partum. Development of responses to exogenous agonists was incomplete 2–3 weeks post partum. The development of postganglionic adrenergic responses lagged behind those to exogenous NA. Two to three weeks post partum the NA maximal response was one-third that of adult tissue whereas the response to 16 Hz (highest frequency used) was one-sixth that of adult tissue. The NA threshold concentration was lower in arterial strips of adult animals than it was in those of younger animals. The data suggest that development of functional postganglionic adrenergic innervation of vascular smooth muscle begins late in gestation and continues well after birth; this development is preceded by development of vascular mechanisms involved in the response to several agonists.
On the mechanism of central hypotensive action of clonidine
Authors: Srimal R. C. , Gulati K. , Dhawan B. N.
Published: April 2011

The hypotensive effect of clonidine in anaesthetised (pentobarbitone) cat has been analysed with the help of pharmacological tools. Application of clonidine (0.1%) to the exposed ventral surface of medulla oblongata produced hypotension (28.6%) and bradycardia (18%). Similar application of glycine (5%) and GABA (10%) also lowered the blood pressure of cat by 20.3% and 29.3%, respectively. The hypotension as well as the bradycardia owing to clonidine were significantly (p < 0.01) blocked by similar prior application of atropine methylnitrate (1%) and hemicholinium-3 (HC3, 1%). whereas HC3 pretreatment only insignificantly blocked the hypotension produced by glycine (p > 0.80) and GABA (p > 0.70). Topical application of atropine (1%) also blocked (p < 0.05) the hypotensive effect of clonidine.Intravenous administration of clonidine (50 μg/kg) produced hypotension (34.6%) after an intial hypertensive response and bradycardia (38.8%). The hypotension was significantly (p < 0.01) blocked by pretreatment of the cat with intracerebroventricular atropine (4 mg) or HC3 (0.5 mg). Topical application of atropine (1%) to the ventral surface of medulla also significantly (p < 0.05) reduced the hypotension and bradycardia resulting from intravenous administration of clonidine.It is concluded that an intact cholinergic link in the brainstem is essential for the hypotensive effect of clonidine.
Effect of castration and testosterone treatment on catecholamine metabolism in ventral prostates of normal and chemically sympathectomized rats
Authors: Rastogi R. B. , Agarwal R. A. , Bhargava K. P. , Singhal R. L.
Published: April 2011

In addition to marked atrophy, castration significantly lowered the endogenous contents of norepinephrine, dopamine, and the synthesizing enzyme tyrosine hydroxylase (EC 1.14.16.2) in the rat ventral prostate. Orchidectomy also markedly reduced the total amount of essential amino acid, tyrosine, the precursor of catecholamine. The changes in these constituents seemed to be androgen-dependent since testosterone (50 mg/kg) replacement for 3 days, beginning from the 4th day of castration, restored various parameters related to monoamine metabolism to values seen in normal rats. Intravenous injections of 6-hydroxydopamine resulted in significant decreases in norepinephrine content and tyrosine hydroxylase activity of the ventral prostate of rats killed on the 11th day after the beginning of treatment. In contrast, the endogenous levels of dopamine and tyrosine per prostate were markedly increased after the administration of 6-hydroxydopamine.A group of rats intended to undergo gonadectomy was injected with two doses of 6-hydroxydopamine (50 mg/kg; 12 h apart) 4 days before castration. These animals were subsequently injected with two doses of 6-hydroxydopamine (100 mg/kg; 12 h apart) 1 day after castration (i.e., the 5th day after the first 6-hydroxydopamine treatment) and killed 6 days after gonadectomy (i.e., the 11th day after the first injection of 6-hydroxydopamine). Administration of 6-hydroxydopamine to castrated rats produced changes similar to those seen in animals with intact testicles, except that the magnitude of changes in norepinephrine, tyrosine hydroxylase, and dopamine content was more pronounced. Even though testosterone treatment in orchidectomized rats previously treated with 6-hydroxydopamine significantly increased tyrosine hydroxylase and norepinephrine levels per prostate, it never restored these adrenergic nerve constituents to normal values. However, both dopamine and tyrosine contents were enhanced well above the values seen in normal rats. Our data suggest that intact nerve supply to the prostate may be important in mediation of the effects of testosterone on the metabolism of its various adrenergic nerve constituents.
Effect of the linoleic acid concentration of mother's diet on adenyl cyclase activity of fetal and neonatal rat brown adipose tissue
Authors: Cresteil Thierry
Published: April 2011

An adenyl cyclase activity was measurable in the brown adipose tissue of fetal rat, and could be stimulated in vitro by noradrenaline during the last 3 days of fetal life. The stimulating effect of noradrenaline was maximal at birth and decreased during the first days of extrauterine life.Ingestion by mothers of a high lipid diet modified the developmental pattern of fetal adenyl cyclase. The linoleic acid content of mother's diet had no effect on the noradrenaline- or fluoride-stimulated specific activities except on the day 22 of gestation. Relative noradrenaline-stimulated activity, expressed as a fraction of the maximal activity, was significantly increased in fetuses and 1-day-old newborns from mothers fed a high linoleic acid diet, but no effect was observed in suckling newborns.
Participation of central noradrenergic neurons in experimental hypertension
Authors: Ameringen Marie-Reine van , Champlain Jacques de , Imbeault Solange
Published: April 2011

A hyperactivity of both the peripheral sympathetic fibers and the adrenal medulla has been shown to be in part responsible for an elevation of blood pressure in rats made hypertensive with DOCA and sodium. Such a generalized activation suggested that the primary dysfunction responsible for this peripheral sympathetic hyperactivity could be localized at a higher level of the blood pressure regulatory mechanism. The norepinephrine turnover rate was studied after blockade of the biosynthesis with α-methyl-p-tyrosine in various regions of the central nervous system. The norepinephrine turnover was found to be increased in most vascular peripheral organs, whereas it was significantly reduced in the brain stem of hypertensive animals compared with that in normotensive animals. On the other hand, the turnover rate was found normal in the spinal cord and in the telediencephalic portion of the brain. The section of the spinal cord at C6–C7 level resulted in a rapid fall in blood pressure within normotensive levels in hypertensive animals while the norepinephrine turnover was restored to normal in peripheral organs. However, the norepinephrine turnover rate remained markedly reduced in the brain stem of these spinalectomized hypertensive rats despite the lowering in blood pressure, thus indicating that the changes observed in the function of catecholaminergic neurons of the brain stem are not secondary to the elevation of blood pressure but could rather be a determinant factor in the induction of the peripheral sympathetic hyperactivity in this form of experimental hypertension.
Glass electrode measurement of net Na+ and K+ fluxes in erythrocytes of the spontaneously hypertensive rat
Authors: Friedman Sydney M. , Nakashima Miyoshi , McIndoe Rosemary A.
Published: April 2011

The exchange of Na+ and K+ in rat red cells at 40% hematocrit incubated in a physiological salt solution containing 1 mM ouabain was monitored with ion-specific glass electrodes. Because this system measures a change in the activity of an ion as a logarithmic function of its preexisting level, Δ[K+]0 is more accurately measured than Δ[Na+]0; within this limitation, the downhill ion movements were close to 1:1 over the temperature span from 37 to 3 °C. These transmembrane movements are reasonably well expressed in terms of first-order kinetics and an Arrhenius plot constructed for K+ as the accurate indicator of the exchange yields an activation energy of 12 kcal/mol. A well-defined reversal of the usual direct relation of temperature to exchange rate was observed between 6 and 3 °C. The net ion movements were distinctly faster at low temperature in cells from rats with spontaneous hypertension (SHR-Okamoto) than in cells from matched controls (Woodlyn and WKY).
Increased response of adipose tissue of the ob/ob mouse to the action of adrenaline after treatment with thyroxin
Authors: Bégin-Heick N. , Heick H. M. C.
Published: April 2011

The activity of the lipolytic system of the obese hyperglycemic mouse was assessed after treatment with physiological doses of thyroxin (T4). The treatment significantly increased fatty acid mobilization in response to adrenaline over the levels observed in the control mice under all conditions studied. The activities of the high- and low-Km phosphodiesterases and of adenylate cyclase were also studied. Treatment of the ob/ob mice with T4 had little effect on the activities of the cyclic AMP phosphodiesterases (high and low Km) but it partially restored the activity of adenylate cyclase, which is deficient in these animals. A correlation was found in the T4-treated obese animals between the ability of the epididymal adipose tissue to mobilize fatty acids, its ability to increase the intracellular levels of cyclic AMP, and the activity of adenylate cyclase in response to adrenaline stimulation.
The effects of changes in inspired oxygen concentration on the experimental production of pulmonary edema in the dog with chronic left ventricular overload
Authors: Baumber John S.
Published: April 2011

A twofold increase in left ventricular output was achieved by suturing a Teflon graft between the aorta and left atrium in dogs. Three weeks after surgery the animals were anesthetized and found to have left ventricular end-diastolic pressures averaging 36 mmHg with markedly elevated right ventricular systolic pressures (RVSP). Oxygen breathing resulted in a decrease in left ventricular pressures, RVSP, and arterial pressure in those animals which survived hypoxia. Fifty percent of the shunted dogs subsequently developed fatal pulmonary edema when allowed to breathe 10% oxygen in nitrogen. These animals showed no change in left ventricular function or pulmonary artery pressure (RVSP) in response to pure oxygen administration. It is suggested that there is a gradation of hemodynamic response to pure oxygen depending on the severity of left ventricular overload. In the severest cases the 'fixing' of pulmonary hypertension may be due to neurohumoral mechanisms. The subsequent development of pulmonary edema in these animals with hypoxia either involves a change in permeability or a redistribution of hydrostatic pressures within the pulmonary vasculature.
Differential effect of D-glucose anomers on proinsulin biosynthesis by the pancreatic islets
Authors: Zucker Peter F. , Lin Boniface J.
Published: April 2011

Pancreatic islets of Langerhans of the rat were used to study effects of D-glucose anomers on the incorporation of [3H]leucine into proinsulin and other islet proteins. At low (1 mg/ml), but not at high (2 mg/ml) glucose concentration, the α-anomer stimulated more proinsulin biosynthesis than the β-anomer. This observation adds to the growing list of islet functions showing anomeric preference for α-D-glucose.
Opiate-like naloxone-reversible actions of somatostatin given intracerebrally
Authors: Rezek M. , Havlicek V. , Leybin L. , Labella F. S. , Friesen H.
Published: April 2011

The latency to tail-flick response in the rat was significantly prolonged by cerebro-ventricular infusion of 1.0 μg of somatostatin (SRIF) and more so with 10.0 μg. The D-tryptophan analog was less effective than native SRIF. Pretreatment with naloxone eliminated analgesia but not seizures induced by SRIF. Recording of the EEG activity enabled determination of the specific state of the sleep–waking cycle in which the repeated tail-flick responses were tested: latency was generally longer in both control and test animals when tail immersion was performed during the state of sleep or drowsiness rather than during the awake state. Although animals receiving SRIF were less likely to fall asleep between subsequent test trials, the average latency was actually longer than after control saline infusion when the animals slept more. SRIF, unlike other releasing factors and peptides tested, showed significant activity in an opiate radioreceptor assay. The blockade of SRIF action by naloxone pretreatment, along with binding of SRIF to opiate receptors in vitro, suggest opiate receptors to be involved in the mediation of analgesia observed in present study.
Alteration of the erythrocyte ultrastructure and blood viscosity by morphine
Authors: Vadas E. B. , Hosein E. A.
Published: April 2011

The effects of acute morphine administration on intact erythrocytes and on their flow properties were studied by measuring the mean cell volume, cell geometry, and whole blood and plasma viscosities. Morphine caused a small (2–7%) increase in mean cell volume. Changes in cell geometry were found to be time dependent and most pronounced in concave portions of the red cells. Whole blood viscosity was found to decrease upon morphine treatment; this may be due in part to a concurrent decrease in plasma viscosity.