bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenosine A1 receptors are located predominantly on axons in the rat hippocampal formation
Authors: Swanson Thomas H. , Drazba Judith A. , Rivkees Scott A. 
Published: January 2005

AbstractThe nucleoside adenosine exerts potent biological effects via specific receptors, including the inhibitory Al adenosine receptor (A1AR). In the hippocampus A1ARs play an important role in regulating neuronal activity. However, the cellular sites of hippocampal A1ARs are undefined. Using in situ hybridization, receptor autoradiography, and single‐ and double‐label immunocytochemistry techniques, we have characterized the cellular sites of A1AR expression in the rat hippocampus. In situ hybridization and receptor autoradiography studies revealed strikingly different patterns of labeling. In situ hybridization studies revealed heaviest labeling of cell bodies in the granular layer of the dentate gyrus and the pyramidal layers of Ammon's horn. In contrast, using [3H] we observed heavy specific labeling over the neuropil in the dentate hilus stratum moleculare, stratum lacunosum‐inoleculare, stratum radiatum, and stratum oriens, and little labeling over cell bodies. Using single‐label immunocytochemistry, A1AR immunoreactivity was found to be heaviest over fibers in regions corresponding with heavy [3H] labeling. Double‐label florescent confocal microscopy was then used to determine the identity of labeled fibers. A1AR immunoreactivity was found to co‐localize with SMI‐31 that labels axons, but not with MAP2a, b that labels cell bodies and dendrites, orwith synaptophysin that labels synapses. These data identify axons as the predominant site of A1AR expression in hippocampus. Activation of A1ARs may be a powerful mechanism by which adenosine alters axonal transmission to inhibit neurotransmitter release. © 1995 Wiley‐Liss, Inc.
Neurochemical subdivisions of the inferior pulvinar in macaque monkeys
Authors: Gutierrez C. , Yaun A. , Cusick C. G. 
Published: January 2005

AbstractThe architecture of the pulvinar of rhesus monkeys was investigated by acetylcholinester ase (AChE) histochemistry, and by immunocytochemiatry for calbindin‐D28k and the SMI‐32 antibody. The presence of four inferior subdivisions, comparable to those found in architectonic connectional studies in squirrel monkeys (C. G. Cusick, J Scripter, J. G. Darensbourg, and J. T. Weber, 1993, J. Comp. Neurol. 336:1–30), provided a basis for a proposed revised terminology for visual sectors of the macaque pulvinar. In the present study, the inferior pulvinar (PI) was identified as a neurochemically distinct region that included the traditional cytoarchitectonic nucleus PI and adjacent portions of the lateral and medial pulvmar nuclei, PL and PM. In calbindin‐D28k stains, the lateral. subdivision of the inferior pulvinar (PIL) had less intense neuropil staining than the adjacent central division, PIc. The PIL was characterized by large, intensely immunopositive neurons seldom found within Plc. PIL occupied the traditional PL and PI and exhibited a shell zone, PIL‐S, restricted to PL. The medial division of the inferior pulvinar (PIM) was in a location previously shown to be strongly connected with the middle temporal visual area (MT) in macaques. PIM was found in the medial one‐half of the traditional PI and extended into adjacent portions of the traditional PM and PL. PIM was distinguished by less intense staining for calbindin and many cells stained with the SMI‐32 antibody for neurofilament protein. In AChE stains, PIL was moderately dark, Plc appeared lighter, and PIM was characterized by small, intensely stained patches. The small posterior division (PIP) stained darkly for calbindin, lightly for AChE, and was unstained with the SMI‐32 antibody. Thus, neurochemical, and perhaps connectional, subdivisions exist within PI, the region of the pulvinar that relays information to striate, “lower order” extrastriate, and inferotemporal visual cortex. © 1995 Wiley‐Liss, Inc.
Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys
Authors: Carmichael S. T. , Price J. L. 
Published: January 2005

AbstractPrevious studies have shown that the orbital and medial prefrontal cortex (OMPFC) is extensively connected with medial temporal and cingulate limbic structures. In this study, the organization of these projections was defined in relation to architectonic areas within the OMPFC. All of the limbic structures were substantially connected with the following posterior and medial orbital areas: the posteromedial, medial, intermediate, and lateral agranular insular areas (Iapm, Iam, Iai, and Ial, respectively) and areas 11m, 13a, 13b, 14c, and 14r. In contrast, lateral orbital areas 12o, 12m, and [12] and medial wall areas 24a, b and 32 were primarily connected with the amygdala, the temporal pole, and the cingulate cortex. Data were not obtained on the poateroventral medial wall.Three distinct projections were recognized from the basal amygdaloid nucleus: (1) The dorsal part projected to area 121; (2) the ventromedial part projected to most areas in the posterior and medial orbital cortex except for areas Iai, 12o, 13a, and 14c; and (3) the ventrolateral part projected to orbital areas 12o, Iai, 13a, 14c, and to the medial wall areas. The accessory basal and lateral amygdaloid nuclei projected most strongly to areas in the posterior and medial orbital cortex. The medial, anterior cortical, and central amygdaloid nuclei and the periamygdaloid cortex were connected with the posterior orbital areas.The projection from the hippocampus originated from the rostral subiculum and terminated in the medial orbital areas. The same region was reciprocally connected with the anterornedial nucleus of the thalamus, which received input from the rostral subiculum. The parahippocampal cortical areas (including the temporal polar, entorhinal, perirhinal, and posterior parahippocampal cortices) were primarily connected with posterior and medial orbital areas, with some projections to the dorsal parr of the medial wall. The rostral cingulate cortex sent fibers to the medial wall, to the medial orbital areas, and to lateral areas 12o, 12r, and Iai. The posterior cingulate gyrus, including the caudomedial lobule, was especially strongly connected with area 11 m. © 1995 Wiley‐Liss, Inc.
Alpha adrenergic receptors and gastric function
Authors: Taylor John A. , Mir G. Nabi 
Published: January 2005

AbstractAlpha‐2 agonists by an effect on alpha‐2 adrenoreceptors in the stomach (and probably in the brain also) suppress vagal nerve acetylcholine release thereby inhibiting gastric motility and secretion and inhibiting the development of gastric lesions in rats in the stress‐, reserpine‐, and cysteamine‐induced ulcer models. Since the effects of the alpha‐2 agonists are consistently inhibited by alpha‐2 blocking agents, their effects appear to be selectively mediated via the alpha‐2 receptor. It seems appropriate therefore that the role of the alpha‐2 receptors be recognized in studies of gastric function and ulcer development.
Central sympathomimetic activity of (+)‐5‐methyl‐10,11‐dihydro‐5H‐dibenzo [a, d]cyclohepten‐5,10‐imine (MK‐801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties
Authors: Clineschmidt Bradley V. , Martin Gregory E. , Bunting Patricia R. , Papp Nan L. 
Published: January 2005

AbstractMK‐801 at doses < 100 μg/kg given orally induced an ipsilaterally directed directed rotational response in rats with a unilateral nigrostriatal lesion produced by 6‐hydroxydopamine. (+)‐Amphetamine, amfonelic acid, and methylphenidate also evoked ipsilateral turning with their dose‐response lines lying considerably to the right of that for MK‐801. Rotations caused by a standard test dose of 50 μg/kg of MK‐801 were reduced by pretreatment with haloperidol (ED50 = 0.068 mg/kg IP), clozapine (ED50 = 3.35 mg/kg IP), or prazosin (ED50 = 0.15 mg/kg SC). MK‐801‐induced turning was also inhibited by pretreatment with α‐methyl‐p‐tyrosine (α‐MPT) and blocked by reserpine.Locomotor activity in mice was increased by MK‐801, amfonelic acid, (+)‐amphetamine, and methylphenidate. Following administration p.o., MK‐801 was the most potent in this regard and methylphenidate the least. Stimulation of locomotor activity by equivalent doses of the four compounds was differentially affected by pretreatment with α‐MPT or reserpine, Reserpinization abolished the increase in activity usually produced by MK‐801, amfonelic acid and methylphenidate, whereas (+)‐amphetamine was only partially (36%) inhibited. Locomotor stimulation by (+)‐amphetamine was, on the other hand, markedly reduced in α‐MPT‐pretreated mice, while the actions of the other three compounds were not singnificantly altered. The ability of all four compounds to increase motor activity was significantly antagonized by haloperidol, but prazosin at the dose (3 mg/kg SC) examined was an effective antagonist of only MK‐801 and (+)‐amphetamine.MK‐801 has effects in rodents resembling indirect‐acting central sympathomimetic substances such as amfonelic acid, (+)‐amphetamine, and methylphenidate. The central sympathomimetic actions of MK‐801 are mediated via catecholamine‐dependent processes. Results from the drug‐interaction studies in mice (locomotor activity) indicate that the precise mechanism of action of MK‐801 differs from that of the other three compounds.
Antiserotoninergic properties of maprotiline and a new antidepressant, oxaprotiline: Two selective na uptake inhibitors
Authors: Delini‐Stula A. , Bischoff S. , Radeke E. 
Published: January 2005

AbstractAntiserotoninergic effects of maprotiline and its hydroxy derivative oxaprotiline (Ba 49802 B), two selective inhibitors of NA uptake, and clinically active antidepressants were investigated in several functional tests and also in in vivo 3H‐spiperone binding assay in the rat. In some tests comparisons with amitriptyline, mianserin, and fluoxetine, which are antidepressants of different qualities, were also done. After single doses up to 30 mg/kg neither maprotiline nor oxaprotiline inhibited L‐5‐HTP‐induced head twitch in mice or tryptamineinduced paw clonus in the rat. Maprotiline, however, but not oxaprotiline, significantly reduced the hyperthermic response to LSD in rabbits and blocked to nearly 90% the 3H‐spiperone labeled 5‐HT receptors in the rat frontal cortex at a dose of 30 mg/kg. Moreover, maprotiline also reduced the response of mice to L‐5‐HTP after daily administration of 25 mg/kg over 10 days. No change in the responsiveness of mice to L‐5‐HTP was observed after the same treatment with oxaprotiline. In agreement with other observations, mianserin and amitryptiline displayed clear‐cut antiserotoninergic effects, whereas fluoxetine potentiated the effects of tryptamine and LSD. The results of this study indicate that, although chemically closely related, maprotiline and oxaprotiline distinctly differ in respect to their action on 5‐HT receptors. Maprotiline exerts 5‐HT receptor blocking effects that appear to increase upon repetitive administration in mice. Oxaprotiline, by contrast, is devoid of them. Comparative experimental and clinical investigations of maprotiline and oxaprotiline may, therefore, provide a clue as to the importance of 5‐HT receptor blocking properties for antidepressant profile of action of drugs.
The antiulcer and antisecretory activity of WHR‐1370A 1‐n‐butoxy‐3‐(2,6 dimethylphenylcarbamoyl) guanidine hydrochloride
Authors: Taylor J. A. , Eash J. R. , Nabi Mir G. 
Published: January 2005

AbstractWHR‐1370A in the rat reduces volume (ED50 = 1.3 mg/kg p.o.) acidity (1.8 p.o.), and pepsin (2.8 p.o.) in the 4‐hr pylorus ligation model, delays gastric emptying (0.75 p.o.), and protects against the development of stress (18‐hr restraint)‐, indomethanic‐, aspirin‐, reserpine‐, and cysteamine‐induced ulcers (ED50s: 10.0 s.c., .65 p.o., 0.59 p.o., 3.0 p.o., and 8.0 s.c., respectively); also WHR‐1370A can completely suppress the cysteamine‐induced rise in serum gastrin. In the pylorus‐ligated rat, the activity of WHR‐1370A is not appreciably altered by methysergide, pimozide, propranolol, corynanthine, or phentolamine but is significantly and competitively antagonized by yohimbine. The pharmacological basis of WHR‐1370A probably can be attributed to an alpha‐2‐mediated inhibition of acetylcholine release at vagal nerve endings.
Central GABA‐ergic systems and analgesia
Authors: Defeudis F. V. 
Published: January 2005

AbstractRecent studies regarding the relationship between GABA‐ergic systems and analgesia have been reviewed and analyzed. It seems evident that central GABA‐ergic systems are involved in opiate‐mediated analgesia since oral or parenteral administration of agents that elicit increases in GABA content of the CNS can enhance the actions of opiates (e.g., morphine). Also, oral or parenteral administration of GABA‐agonists (e.g., 4,5,6,7‐tetrahydroisoxazolo[5,4‐c]‐pyridin‐3‐ol; THIP), inhibitors of GABA‐α‐oxoglutarate transaminase (e.g., γ‐vinyl‐GABA), or GABA uptake inhibitors (e.g., nipecotic acid ethyl ester) can produce analgesia. As the analgesia produced by agents that enhance central GABA‐ergic mechanisms is not reversed by naloxone, its further study might lead to the development of centrally active analgesic drugs that do not produce physical dependence/tolerance in man.
Mescaline‐induced head‐twitches in the rat: An in vivo method to evaluate serotonin S2 antagonists
Authors: Niemegeers C. J. E. , Colpaert F. C. , Leysen J. E. , Awouters F. , Janseen P. A. J. 
Published: January 2005

AbstractAn intravenous dose of 20.0 mg/kg of mescaline induced a reproducible head‐twitch response in rats. Drugs with very different pharmacological activities were tested for potential inhibition of this response. Among these drugs were a large number of serotonin antagonists, including several members of the recently described selective S2 antagonists of which ketanserin (a potent vascular S2 antagonist) and pirenperone (a pure LSD antagonist) are two prototypes. The same compounds were further studied in six in vivo tests in rats; these tests presumably measure antagonism at sites responsive to serotonin, dopamine, norepinephrine, histamine, or acetylcholine. A large number of test compounds inhibited mescaline‐induced head‐twitches. Although it was often associated with it, this activity did not correlate with any of the following effects: antagonism of apomorphine, norepinephrine, compound 48/80, physostigmine, or with mydriatic activity. Antagonism of mescaline did correlate, however, with in vivo antagonism of tryptamine and 5‐hydroxytryptophan, and with inhibition of 3H‐spiperone binding to the rat prefrontal cortex in vitro. It is concluded that inhibition of mescaline‐induced head‐twitches in the rat is a valid measure of serotonin S2 antagonist activity, also for those compounds whose primary activity occurs at dopamine, norepinephrine, histamine, or acetylcholine receptors. Ketanserin, pirenperone, and several chemically related compounds are very potent mescaline antagonists.
Potentiation of yohimbine‐induced lethality in mice: Predictor of antidepressant potential
Authors: Malick Jeffrey B. 
Published: January 2005

AbstractThe ability of antidepressant agents to potentiate the lethal or toxic effects of yohimbine in mice was evaluated. With very few exceptions, the antidepressants were the only agents that significantly enhanced yohimbine‐induced lethality. All of the clinically effective antidepressants, both typical (e.g., amine reuptake inhibitors, monoamine oxidase inhibitors) and atypical (e.g., mianserin, iprindole, bupropion, quipazine) drugs, produced a dose‐related potentiation of yohimbine in mice. Representative anxiolytics and antipsychotics failed to potentiate yohimbine over a wide range of doses. Although several possible “false positives” (e.g., atropine, chlorpheniramine, and d‐amphetamine) would be detected in this procedure, these same agents would be detected in other models (e.g., tetrabenazine antagonism, behavioral despair) considered predictive of antidepressant potential. Thus, the potentiation of yohimbine‐induced lethality test in mice appears to represent a useful screening procedure for discovering potential antidepressant drugs.
Effect of clonidine on responsiveness of venous smooth muscle to sympathetic neurotransmitter
Authors: Wood William B. , Sticht Frank D. , Cardoso Sergio S. , Elko Edward E. 
Published: January 2005

AbstractThe presence of both longitudinal and circular smooth muscle makes the canine accessory cephalic vein a sensitive preparation for the evaluation of venomotor activity. Infusion of clonidine (10 μg/kg) into this intact, peripheral vein results in transient, localized venoconstriction and prolonged arterial hypotension. Bradycardia, paralleling the hypotension in onset and duration, is a consistent concomitant. Exposure of the test vein smooth muscle to clonidine diminishes responsiveness of this vein to subsequent close injections of norepinephrine. This inhibition, though pronounced, is short‐lived and usually abates within an hour.
Effect of prazosin on veins: Inhibition of norepinephrine venoconstriction in dog forelimb
Authors: Sticht Frank D. , Wood William B. , Cardoso Sergio S. , Elko Edward E. 
Published: January 2005

AbstractA dose–response curve was established based on increases in venous infusion pressure evoked by injection of a series of small doses of norepinephrine, before and after slow infusion of a prazosin solution into the accessory cephalic vein of anesthetized dogs. During the prazosin infusion, there was an increase in venous infusion pressure, which returned to control levels by the end of the infusion period. The reduction in arterial pressure that occurred during the infusion persisted throughout the experiment. Immediately following the prazosin infusion, venous constrictor responses to norepinephrine were greatly inhibited, an effect that was still present 1 hr later. Prazosin has a marked in vivo α‐adrenergic receptor inhibiting action in the accessory cephalic vein of the dog. This effect may be preceded by an agonistic action on these receptors at this site, as suggested by the increase in venous infusion pressure during the period of prazosin administration.
Buspirone as a midbrain modulator: Anxiolysis unrelated to traditional benzodiazepine mechanisms
Authors: Eison Michael S. , Eison Arlene S. 
Published: January 2005

AbstractBuspirone is a clinically effective anxiolytic unrelated to the benzodiazepines in structure and pharmacological properties. Recent mechanism of action studies suggest that rather than working through traditional benzodiazepine mechanisms, buspirone affects diverse aspects of the brain's neurochemical circuitry. It acts as a presynaptic dopamine antagonist with little potency at postsynaptic dopamine sites. This action may synergize with a GABA antagonist component to its action to alter activities in diverse brain systems. These actions can be hypothesized to relate to buspirone's behavioral effects: GABA (catalepsy reversal), corticostriatal glutarnate (stereotypy), acetylcholine (EEG activation and enhanced psycho‐motor performance), and mesolimbic, mesocortical dopamine in addition to midbrain norepinephrine and serotonin (anxiolysis). A hypothetical scheme of buspirone's effects on the brain based upon already established elements of its mechanism of action is presented. This scheme suggests that buspirone's unique anxioselective profile is derived from complex polysynaptic actions and their ramifications upon multiple neural substrates that collectively mediate anxiety.
A double‐blind clinical trial of fluvoxamine and imipramine in patients with primary depression
Authors: Guy William , Wilson William H. , Ban Thomas A. , King Douglas L. , Manov Gregory , Fjetland Olaf K. 
Published: January 2005

AbstractFluvoxamine, a new serotonin‐reuptake inhibitor, and imipramine were compared under double‐blind conditions in 36 unipolar and bipolar depressed inpatients. Both drugs produced significant reductions in depressive symptomatology over a 4–6‐wk course of treatment, with the greater part of the improvement occurring in the first 2 wk. No statistically significant differences were obtained between the two drugs. Adverse reactions, particularly anticholinergic ones, were much less frequently observed in the fluvoxamine group. No clinically significant laboratory abnormalities were reported for either treatment; but minor ECG irregularities were seen under both treatments. The findings generally correspond to results obtained in previous comparative clinical trials.
The toxicology of the schistosomicidal agent oxamniquine
Authors: Chvédoff M. , Faccini J. M. , Gregory M. H. , Hull R. M. , Monro A. M. , Perraud J. , Quinton R. M. , Reinert H. H. 
Published: January 2005

AbstractOxamniquine displayed low acute toxicity in mice, hamsters, and rabbits. In rats, however, oxamniquine was much more toxic, the female being 8–10 times more sensitive than the male; single doses elicited an idiosyncratic sex‐linked hepatic necrosis and bile duct proliferation. Dogs given repeated oral doses of 20 or 30 mg/kg/day for 5 successive days every 4 weeks for 11 months showed neurological disturbances of short duration, which tended gradually to increase in severity from one dosage period to the next; no histopathological correlate could be found. In chronic studies in mice (18 months) and hamsters (19 months) with intermittent dosage regimens relevant to likely usage in man, no evidence of carcinogenicity potential was observed at dose levels up to 150 mg/kg. Oxamniquine displayed no maternal toxicity or teratogenicity in mice and rabbits, and only slight embryotoxicity after high oral doses.
Modulators of intracellular calcium
Authors: Winquist Raymond J. 
Published: January 2005

AbstractThe importance of calcium in excitation‐contraction coupling in both cardiac and vascular smooth muscle has resulted in an intense research interest into the intracellular regulation of this ion. Selective foci for the modulation of intracellular calcium include the interaction of calcium with the contractile protein apparatus, sites of calcium release and sequestration, and pathways for the extrusion of calcium into the extracellular space. Research efforts directed towards elucidating these phenomena have met with varied degrees of success. The presence of different calcium regulatory systems for contractile protein function, i.e., troponin in cardiac and calmodulin‐myosin light chain kinase in vascular, provides an attractive rationale for the design of selective compounds. The inherent difficulty in studying intracellular release and sequestration presently presently precludes examining the physiological implications of specific inhibition of these phenomena. However, the apparent absence of a sodium‐dependent calcium extrusion pathway in vascular tissue may lead to the design of novel cardiotonics. It is anticipated that further clarification of the similarities and differences in the calcium cycle between these tissues will result in the development of tissue‐selective therapeutic agents.