bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasopressin binding in the cerebral cortex of the mongolian gerbil is reduced by transient cerebral ischemia
Authors: Vallet Philippe , Bouras Constantin , Barberis Claude , Dreifuss Jean Jacques , Dubois‐Dauphin Michel 
Published: January 2005

AbstractIn Mongolian gerbils, the content of vasopressin in the cerebral cortex, the striatum, and the hypothalamus is increased after induction of acute cerebral ischemia. We used an iodinated vasopressin analogue and light microscopic autoradiography to study the distribution of vasopressin V1 receptors in the brain of adult male gerbils and to evaluate the effects of a transient bilateral cerebral ischemia (6 minutes) on the density of this receptor population. The animals were killed immediately or 10, 30, or 100 hours after transient bilateral occlusion of the common carotid arteries.In control animals, specific [125I]‐VPA binding sites were present in various structures of the brain (olfactory bulb, anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis, median preoptic area, ventral pallidum, substantia innominata, amygdala, thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling was detected in the cerebral cortex, layers 5–6. After 30–100 hours of survival time following ischemia there was a marked decrease in [125I]‐VPA binding site density in these cerebral cortex layers. To a lesser degree, a decrease was also detected in the lateral septal nucleus. In contrast, labeling in other noncortical structures remained unchanged. All animals with 100 hours recovery showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition, ischemia induced concomitant and proliferative changes in cortical and hippocampal astrocytes assessed by glial fibrillary acid protein immunoreactivity. These observations indicate a role for vasopressin in the cerebral cortex either on neurons or on glial cells and the modulation of vasopressin receptor expression by transient cerebral isehemia. © Wiley‐Liss, Inc.
Comparison of the topology and growth rules of motoneuronal dendrites
Authors: Dityatev Alexander E. , Chmykhova Nadejda M. , Studer Lorenz , Karamian Olga A. , Kozhanov Valery M. , Clamann H. Peter 
Published: January 2005

AbstractThe complexity, shape, and branching modes of the dendrites of spinal motoneurons were compared in cat, rat, and frog using topological analysis and growth models. The complexity of motoneuronal dendrites, measured as the mean number of terminal segments, varied significantly among samples and was related to contractile properties of innervated motor units. Despite this variation, all mature motoneurons having a mean number of terminal segments per dendrite greater than ten (up to 24. 3) exhibited a narrow range of values of coefficients describing the symmetry of tree shapes (0.42–0.47). This implies low variability in the topological shape of motoneuronal dendrites of different animals. This similarity of tree shapes proved to be a result of the similarity of growth rules. The growth of the dendrites could be described to a first approximation by a two‐parameter (Q and S) model called the QS model and by a multitype Markovian model. The estimation of parameters of the QS model, in which parameter Q is related to the probability of branching of intermediate segments, revealed that Q was equal or close to 0, implying that branching of dendrites is restricted to terminal segments. The estimates of the parameter S, which describes whether the probability of branching increases (S < 0) or decreases (S > 0) exponentially with segment order, were positive. This was in agreement with the results of estimation of probabilities of branching provided by the Markovian model, which showed that the branching probabilities decreased with segment order in an exponential manner in most of the neurons studied.The QS and Markovian models involve different assumptions about the sequence and timing of branching events, and selection of the best model can provide insight into details of dendritic outgrowth. Extensive simulation of tree outgrowth using a Markovian model revealed significant differences between simulated trees and real dendrites, particularly with regard to variability of the number of terminals and to symmetry. In contrast, the QS model provided a good fit to the mean values and standard deviations of basic topological parameters. This model is adequate to describe the shape of mature motoneurorial dendrites. It implies that dendritic branches have many opportunities to bifurcate during the whole time of development and that bifurcating potency of a branch is a function of the number and position of other branches of that dendrite. Combined with analysis of metrical properties such as lengths of segments, the QS model can assist in a quantitative analysis of development and plasticity. © 1995 Wiley‐Liss, Inc.
A comparison of the antidiarrheal and some other pharmacological effects of clonidine, lidamidine, and loperamide in the rat
Authors: Lal Harbans , Shearman Gary T. 
Published: January 2005

AbstractClonidine, lidamidine, and loperamide each inhibited castor oil‐induced diarrhea in the rat. Clonidine and lidamidine, but not loperamide, also induced diuresis but at doeses above those producing antidiarrheal activity. Clonidine and lidamidine, but not loperamide, produced autonomic and central effects including piloerection, hypotonia, exopthalmus and ataxia at doeses similar to those producing antidiarrheal activity. These data suggest that only loperamide possesses selective antidiarrheal activity.
Suppression of insulin‐induced prolactin secretion in man by nomifensine
Authors: Masala Antonic , Alagna Sergio , Rovasio Pier Paolo , Rassu Sergio 
Published: January 2005

AbstractIn 12 healthy male volunteers we studied the effect of nomifensine, an inhibitor of endogenous catecholamine reuptake, on insulin‐induced prolactin and growth hormone (GH) secretion. The effect of the drug on TRH‐induced prolactin secretion was also studied. Nomifansine was able to suppress completely the insulin‐stimulated prolaction secretion, whereas no effect on GH secretion was observed. TRH‐induced prolactin secretion was uninfluenced by the drug.
Thyroliberin (TRH)‐induced shaking behavior in rats: Inhibition by antinociceptive compounds
Authors: Kruse Hansjoerg , Moeller Juergen 
Published: January 2005

AbstractThe influence of 49 compounds, among them 12 analgesics, on “wet dog” shaking (WDS) induced by thyroliberin (TRH) in rats has been investigated. WDS was dose dependently reduced by all of the analgesics and by 20 of the other drugs. The following compounds were the most active (ED50 values in parentheses): clonidine (5.4 μg/kg), fentanyl (9.6 μg/kg), oxotremorine (21 μg/kg), apomorphine (0.25 mg/kg), amphetamine (0.30 mg/kg), tetrabenazine (0.38 mg/kg), morphine (0.78 mg/kg), chlorpromazine (1.0 mg/kg), and ergotamine (1.2 mg/kg). Both agonists and antagonists of noradrenergic, dopaminergic, serotonergic, and GABA‐ergic functions were inhibitors of WDS, and antinociceptive activity was shared by most of the effective drugs.Thus, WDS or head‐shaking induced by TRH must be considered to be an expression of headache rather than such other causes as heat gain mechanisms or tremor induction. Prevention of TRH‐induced WDS may be used as a test of analgesic activity.
Attenuation of conflict‐induced suppression by clonidine: Indication of anxiolytic activity
Authors: Kruse Hansjoerg , Dunn Robert W. , Theurer Karin L. , Novick William J. , Shearman Gary T. 
Published: January 2005

AbstractClonidine was tested in a conflict‐induced suppression paradigm (bar pressing for food reward suppressed by electric foot shock) in rats. This drug significantly and dose dependently (25–100 μg/kg) both increased punished responding and decreased unpunished responding. Clonidine at 200 μg/kg had no effect on punished bar pressing, although it markedly inhibited unpunished responding due to sedation. The effect of clonidine on shock‐suppressed lever pressing was prevented by yohimbine 5 mg/kg and partially antagonized by phenoxybenzamine 2.5 mg/kg but was not significantly altered by phenoxybenzamine 1 mg/kg, atropine 5 mg/kg, methysergide 5 mg/kg, or naloxone 10 mg/kg.This activity of clonidine does not seem to be due to its analgesic or food intake‐increasing properties. It may be a true anxiolytic effect, brought about by presynaptic stimulation of noradrenergic neurons which could result in an inhibitory influence on the locus coeruleus.
Dopaminergic activity of some simplified ergoline derivatives
Authors: Euvrard Catherine , Ferland Louise , Fortin Michel , Oberlander Claude , Labrie Fernand , Boissier Jacques R. 
Published: January 2005

AbstractThe dopamine (DA) agonist activity of new simplified ergoline derivatives (RU 27849, RU 28251, and RU 28306) was studied in comparison with bromocriptine. In contrast to bromocriptine, the three compounds were weak displacers of 3H‐dihydroergocriptine or 3H‐spiroperidol binding from bovine anterior pituitary or rat striatal membrane sites and weak inhibitors of prolactin secretion in anterior pituitary cells in culture. Similarly to bromocriptine, they did not induce changes in either the basal or the DA‐induced stimulation of the adenylate cyclase activities. In vivo, the three derivatives, at a low dose, increased plasma prolactin levels, decreased striatal DA turnover, and increased striatal acetylcholine content, as did bromocriptine. Furthermore, in 6‐OHDA‐lesioned rats, these molecules, like bromocriptine, induced an intense contralateral circling behavior. From their effectiveness in these different tests, the potencies of these new ergoline derivatives can be ranked in the following order : N‐propyl > N‐methyl > N‐H.
Influence of age on isolation stress‐stimulated carcinogen‐metabolizing enzymes of rats
Authors: Capel I. D. , Jenner M. , Dorrell H. M. , Williams D. C. 
Published: January 2005

AbstractRats aged 6, 12, 24, 36, and 52 weeks were subjected to social isolation for 4 days, while littermates housed in groups of six for the same period served as controls. The isolation treatment resulted in a 2‐fold increase in the serum corticosterone level of all except the youngest animals in whom the hormone level was greater than 4 times that of their age‐matched controls. Hepatic microsomal protein was highest in the 24‐week‐old rats and lowest in the rats aged 52 weeks. The levels of most of the enzymes measured were lowest in the 6‐ and 52‐week‐old animals. No significant differences in microsomal protein, cytochrome P450, epoxide hydrolase, UDPGA transferase, or glutathione transferase were observed between the isolated and control animals. The stress treatment increased aryl hydrocarbon hydroxylase levels of the rats aged 6, 36, and 52 weeks by 100%, 50%, and 33% respectively. The microsomes prepared from livers of isolated 6‐week‐old animals catalyzed the binding of significantly higher amounts of [3H]‐benzo(a)pyrene to DNA than controls.
The clinical relevance of opiate receptor research
Authors: Smith Andrew P. , Loh Horace H. 
Published: January 2005

AbstractRecent progress in opiate receptor research of particular relevance to clinicians is discussed. A simple binding assay, which in itself is valuable in allowing rapid screening of new compounds for opiate activity, has been the basis of these studies. Extensive mapping of opiate receptors in subcortical brain regions has provided important insights into the neuronal pathways involved in analgesia, while physical and chemical characterization of these receptors has led to a simple means of distinguishing agonists from antagonists. The existence of multiple receptors suggests that the analgetic effects of the opiates may be dissociated from other effects, and studies of tolerance and dependence indicate that they too may be dissociable from analgesia. Purification of the receptors, at last a reasonable possibility, may lead to new ways to promote or inhibit analgesia.
Antagonism of baclofen's effects on rat striatal 5‐HT metabolism: A model for 5‐HT agonistic properties?
Authors: Waldmeier Peter C. , Fehr Bruno 
Published: January 2005

AbstractThe increase in the rat striatal concentration of 5‐hydroxyindoleacetic acid (5‐HIAA) elicited by baclofen was antagonized by the 5‐HT antagonists pipamperone (10/30 mg/kg i.p.), cyproheptadine (30 mg/kg i.p.), methiothepin (1 mg/kg i.p.), and GP 50 302 (1/3 mg/kg i.p.), but not by cinanserin (1–30 mg/kg i.p.), pizotifen (1–10 mg/kg i.p.), spiroperdol (0.1–1 mg/kg i.p.), or haloperidol (0.1–1 mg/kg i.p.). The 5‐HT agonists, m‐chlorophenylpiperazine (1 mg/kg i.p.) and MK 212 (3/10 mg/kg i.p.) also showed an antagonistic effect. Methysergide (5–20 mg/kg i.p.) and quipazine (2.5/5 mg/kg i.p.) were previously shown to act similarly, whereas mianserin (5–20 mg/kg i.p.) was inactive and methergoline at lower doses (0.25–0.5 mg/kg i.p.) increased the effect of baclofen, which was reversed at higher doses (1 mg/kg i.p.). The alterations by these compounds of the 5‐HT increase elicited by baclofen were more or less similar; however, they were less clear‐cut and occurred at higher doses. These interactions were not the result of interferences of the compounds with the absorption, distribution, or metabolism of baclofen nor with its effect on the nigrostriatal dopaminergic system, since the increase in dopamine concentrations it caused was not affected by any of the compounds. A comparison of our results with published data on the antagonism of 5‐hydroxytryptophan‐induced head twitches, on spiroperidol or 5‐HT displacement, on 5‐HT‐stimulated adenylate cyclase, and with electrophysiological results suggests that the antagonistic effect of compounds interfering with the 5‐HIAA elevating action of baclofen is not related to 5‐HT receptor blocking properties of these drugs, Instead, it seems to be much more related to 5‐HT agonists properties. It is speculated that this model might reveal presynaptic agonistic properties of drugs, but more data are needed to confirm or reject this.
The cardiovascular effects in dogs of two N‐Di‐Alkyl substituted analogs of dopamine and dopamine
Authors: Maixner W. , Long J. P. , Wright C. B. , Cannon J. G. 
Published: January 2005

AbstractThe cardiovascular effects of two N‐di‐alkyl substituted analogs of dopamine and dopamine were tested in the dog. Intravenous administration of N, N‐diethyldopamine (DEDA) decreased mean arterial pressure, heart rate, and mildly depressed cardiac output. Intravenously administered N, N‐dipropyldopamine (DPDA) decreased mean arterial pressure, heart rate, and total peripheral vascular resistance. Both compounds inhibited reflex sympathetic responses produced by a bilateral common carotid occlusion. Femoral artery injections of DEDA or DPDA produced biphasic responses. A transient increase in femoral bed vascular resistance was followed by a decrease in femoral bed vascular resistance sensitive to alpha adrenoceptor antagonism. In contrast to DEDA and DPDA, intravenously administered dopamine increased cardiac output and heart rate while reducing arterial pressure and total peripheral vascular resistance. Femoral artery injections of dopamine resulted in a dose‐dependent constrictor response which was antagonized by alpha receptor blockade. These data demonstrate that DEDA and DPDA induce different cardiovascular responses from dopamine.
Effects of antidepressants and related drugs on the quantitatively analyzed EEGs of beagles
Authors: Frankenheim Jerry 
Published: January 2005

AbstractPower spectral analysis was applied to beagles' EEGs to determine if clinically effective antidepressants produce changes different from those produced by related drugs. Bipolar EEGs were recorded from screws chronically implanted in the skull 5 mm anterior and 10 mm posterior to bregma, 4 mm left of midline. The normalized spectral estimates obtained after intravenous drug injection (minus the temporally corresponding spectral estimates after saline) were averaged across dogs. Drug effects were related to dose and time. Reliable effects of imipramine, amitriptyline, desipramine, and mianserin were an increase in the percent of power in the 4.5–7.5 Hz (theta) band, an increased percent of power in the alpha band at low doses, a decreased percent of power above 22 Hz (beta‐2), and an increased total spectral absolute power, at doses that produced no symptoms. Chlorpromazine's EEG effects were similar to the antidepressants'. Atropine increased percent theta and decreased percent beta‐1 and beta‐2, but was distinguished from the above drugs since it also increased percent delta and produced symptoms at the lowest effective dose. The other drugs either had no effect on percent theta (physostigmine) or decreased it (chlordiazepoxide, dextroamphetamine, and cocaine); cocaine increased only percent delta. Chlordiazepoxide, dextroamphetamine, and physostigmine increased percent beta‐1 and/or beta‐2, and they either decreased total power (dextroamphetamine) or produced no change in this parameter, and thus were distinguished from antidepressants. The results support the conclusion that antidepressants have distinct acute effects on brain electrical activity, and suggest that novel antidepressants can be detected by EEG spectral analysis in dogs.
A sequential model of pharmacologic assays for evaluating myocardial depressant effects of potential cardiovascular drugs
Authors: Kitzen Jan M. , Schwenkler Mary A. , Moeller Janice E. , Novick William J. 
Published: January 2005

AbstractA model of sequentially arranged pharmacologic assays was developed to evaluate myocardial‐depressant properties of various drugs. The sequence of assays consisted of the following: hemodynamics in normal dogs, hemodynamics in ganglion‐blocked dogs, isolated‐stimulated guinea pig left atria, spontaneously beating guinea pig atria, and an optional follow‐up experiment consisting of hemodynamics in ganglion‐blocked dogs with cardiac pacing. Four reference compounds (clonidine, verapamil, hydralazine, and mixidine) plus a test compound (P79‐4058) were subjected to the test model with the goal of being able to discriminate between various types of myocardial depression. Results from this study indicate that the model was able to separate out three classes of actions: drugs with no depressant activity (hydralazine), drugs that cause myocardial depression indirectly via the nervous system (clonidine), and a third group that elicit myocardial depression directly (verapamil and P79‐4058). Mixidine produced variable results in this model. The proposed model appeared to be adequate in that enough information can be obtained so that new pharmacologic compounds may be evaluated and decisions as to further development can be made.
Effects of N‐substituted analogs of (−)‐α‐acetylmethadol and (−)‐α‐methadol on schedule‐controlled behavior
Authors: McMillan D. E. , Lattin D. L. , Hardwick W. C. , Greene D. L. , Raible P. K. , Richardson J. B. 
Published: January 2005

AbstractThe behavior of the pigeon maintained under a variable‐interval schedule of food presentation was used to compare the activity of four novel N‐substituted acetylmethadol and methadol analogs with that of methadone and (‐)‐α‐acetylmethadol (LAAM). All of the acetylmethadol and methadol analogs had narcotic agonist activity, as defined by the reversibility of their behavioral effects by naloxone. The effect of the N‐substituted analogs on variable‐interval responding was similar to that of methadone and LAAM, but all these compounds had a slower onset of action than methadone and a shorter duration of action than LAAM. None of the N‐substituted analogs showed narcotic antagonist activity when tested against methadone.
The effects of cibenzoline, an imidazoline derivative with antiarrhythmic properties, on systemic hemodynamics and regional myocardial performance
Authors: Verdouw Pieter D. , Hartog Johannes M. , Scheffer Michael G. , Van Bremen Robert H. , Dufour Alain 
Published: January 2005

AbstractThe effects of increasing doses of cibenzoline (‐2(2,2‐diphenylcyclopropyl)‐2‐imidazoline, Cipralan), a new compound with antiarrhythmic properties, on systemic hemodynamics and regional myocardial performance were studied in anesthetized pigs. Doses of 0.5–2.0 mg kg−1 i.v. produced a 10–15% prolongation of the PP' interval, and a dose‐dependent increase (up to 60%) in QRS width, with only minor changes in PQ and ST length. Stroke volume decreased dose dependently (20–35%) immediately after drug administration, due to a decrease in myocardial contractility and an increase in systemic vascular resistance. Renal blood flow was unchanged, despite the decrease in cardiac output. Coronary blood flow decreased, while myocardial O2 extraction was unchanged. Hence myocardial O2 consumption decreased parallel to the decrease in flow, a consequence of the lowered myocardial O2 demand. Studies with radioactively labeled microspheres revealed that the decrease in myocardial blood flow was equally distributed over the transmural layers.
Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation
Authors: Ashton David , Reid Kenneth , Willems Roland , Marrannes Roger , Wauquier Albert 
Published: January 2005

AbstractExposure of hippocampal slices to a medium containing a low Ca2+‐concentration and an increased concentration of Mg2+ and K+ resulted in the blockade of synaptic transmission and the development of spontaneous synchronized epileptiform bursts (SSEB) in area CA1. The SSEBs were measured extracellularly as a negative potential shift with superimposed population spikes. Flunarizine is a “Ca2+‐entry blocker” with antiepileptic actions in humans. We compared flunarizine with two reference antiepileptics (phenytoin and carbamazepine) and two other “Ca2+‐entry blockers” (verapamil and nimodipine) for their ability to reduce SSEBs. Flunarizine, which is insoluble in ACSF bathing medium, was applied in a nanodrop directly onto the CA1 region of the slice. All other drugs were applied in the bathing medium. Flunarizine (1 picomol), phenytoin (2 × 10−5 M), and carbamazepine (5 × 10−6, 5 × 10−5 M) reduced the SSEBs. Nimodipine (1 × 10−5 M) and verapamil (2 × 10−5M) were ineffective. Increases in extracellular K+ occurred synchronously with, and decreases in extracellular Ca2+ followed, negative potential deflections during SSEBs. As the amplitude of potential shifts decreased after flunarizine so did the ion‐shifts. Since changes in Ca2+ and K+ did not occur before changes in potential, modulation of Ca2+ or K+ channels in striatum pyrarnidale is unlikely to explain flunarizine's ability to reduce synchronized bursts. Further, the ability to block Ca2+ channels in the periphery appears to be unrelated to the ability to block SSEBs in this model. It is suggested that reduction of Na+ currents during depolarization may be the basis of the similar effects of phenytoin, carbamazepine and flunarizine in this model.
Triazolo antidepressants do not inhibit monoamine oxidase
Authors: Hyslop Deborah K. , Allen Lloyd E. , Taylor Duncan P. 
Published: January 2005

AbstractThe nontricyclic antidepressant trazodone and the related triazolo antidepressants nefazodone and etoperidone are monoamine uptake inhibitors. We quantified the interaction of these compounds with monoamine oxidases in vitro and in vivo. All three compounds were devoid of activity in these studies. This suggests that the clinical use of trazodone, nefazodone, or etoperidone will not be associated with deleterious dietary interactions seen with monoamine oxidase inhibitor antidepressants.