摘要:

AbstractThe use of the behavioral 5‐HT syndrome in rats to characterize psychoactive drugs interacting with the central serotonin system is described. The potentiation of L‐5‐HTP‐induced excitation can be used to detect drugs inhibiting central monoamine oxidase (MAO) A or the 5‐HT uptake system and to define their mechanism of action. In addition to their potency, the biological half‐life of these types of drugs can also be measured. The mechanism of action by which β‐adrenoceptor agonists like salbutamol or clenbuterol potentiate behavioral effects of L‐5‐HTP is discussed. The 5‐HT syndrome is also a convenient behavioral test system to screen for central 5‐HT antagonists and 5‐HT agonists. Different procedures to characterize the 5‐HT specificity of behavioral effects induced by putative 5‐HT agonists are described a

ISSN:0272-4391    

DOI:10.1002/ddr.430040602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe hypothesis that a DRL schedule requiring a long pause (>72 sec) specifically identifies antidepressant drugs was evaluated in rats pressing a lever for food reinforcement. The tricyclic antidepressant imipramine decreased responses and increased reinforcements as previously shown. However, the antipsychotics chlorpromazine and clozapine had a similar effect, as did prefeeding, and the atypical antidepressant bupropion increased responses and decreased reinforcements. Because mean baseline reinforcement rate was lower than in previous studies showing drug class specificity, the DRL requirement was reduced to>36 sec and the drugs were tested again; effects were qualitatively similar to those in DRL>72 in the first part of the study. The results suggest that a drug‐induced reduction in responses could account for the increase in reinforcements, that if drug class specificity exists it may occur only when baseline response and reinforcement rates are confined to a narrow range, that the failure of previous studies to show antidepressant type effects with nonantidepressants could have resulted from choice of drugs and doses, and that the type of reinforcer could be an important facto

ISSN:0272-4391    

DOI:10.1002/ddr.430040603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe effects of the antihistamines astemizole, ketotifen, and terfenadine, given orally at the dose of 10 mg/kg, were investigated on 16‐hr sleep‐wakefulness patterns in dogs. As determined in the Ascaris allergy test in dogs, this dose had marked antihistaminic activity for at least the total duration of the recording. Using a computerized on‐line analysis and automatic sleep classification, a differentiation was made between wakefulness, transition to sleep, slow‐wave sleep, and REM (or paradoxical) sleep. Astemizole did not significantly change sleep‐wakefulness patterns. Ketotifen significantly increased slow‐wave sleep and significantly decreased REM sleep. Terfenadine significantly decreased wakefulness and significantly increased both slow‐wave sleep and REM sleep. With both ketotifen and terfenadine, REM latency was prolonged. Two different mechanisms appear to be involved in the REM sleep effects seen with terfenadine: an early REM sleep suppressant effect and a late but large REM sleep‐enhancing effect. This study shows central effects of terfenadine that are not completely typical for H1antagonists but which are very pronounced at a dose producing much weaker peripheral antihistamine activity than the same dose of ketotifen

ISSN:0272-4391    

DOI:10.1002/ddr.430040604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractRecent studies in this laboratory have demonstrated that clonidine, a centrally acting antihypertensive drug, can inhibit the function of central cholinergic neurons. We have also provided evidence for enhanced brain cholinergic activity in the spontaneously hypertensive rat (SHR). The purpose of this study was to determine whether the antihypertensive response to clonidine in the SHR could be correlated with a decrease in acetylcholine synthesis in several brain regions. Clonidine (30μg/kg, i.v.) produced a time‐dependent reduction in blood pressure (BP) in unrestrained SHR's of 18/16 and 27/22 mmHg by 10 min and 100 min, respectively. The formation of3H‐acetylcholine in the brain following pulse injection of3H‐choline (20 μCi) into the lateral cerebral ventricle was employed as an estimate of the rate of acetylcholine synthesis. Clonidine produced a time‐dependent inhibition of3H‐acetylcholine formation in several brain areas. For example, in the pons,3H‐acetylcholine formation was reduced by 21 and 44% at 10 min and 100 min following clonidine, respectively. Other brain regions to exhibit significant inhibition of cholinergic activity included the rostral and the caudal hypothalamus, medulla oblongata, thalamus‐septum, and midbrain. The striatum exhibited the greatest3H‐acetylcholine formation in control animals; however, this activity was not affected by clonidine. These results are consistent with the ability of clonidine, at a clinically relevant dose, to elicit concomitantly an antihypertensive response and a marked inhibition of brain cholinergic activity in SHRs. This finding in conjunction with the results from several previous studies suggest that central cholinergic neurons participate in mediating the antihypertensive ac

ISSN:0272-4391    

DOI:10.1002/ddr.430040605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractSpecific binding of (3H)‐dexoxadrol to rat brain membrane was saturable. The specific binding represented 74 to 82% of total binding. Scatchard analysis of the data demonstrated the existence of high‐ and low‐affinity binding sites. The kinetic constants for the corresponding binding sites were as follows: Kd1= 1.68 nM, Bmax1= 0.4 pmol/mg protein, Kd2= 26.1 nM, and Bmax2= 3.7 pmol/mg protein. Binding reached equilibrium within 5 minutes of incubation at 25°C. Optimum binding was observed between the pH range of 7.4 to 9. Binding was dependent on protein concentration and was reduced by denaturation of protein and by proteolytic enzyme. (3H)‐dexoxadrol binding was inhibited by drugs pharmacologically similar to phencyclidine (PCP) and bound (3H)‐dexoxadrol could be rapidly displaced b

ISSN:0272-4391    

DOI:10.1002/ddr.430040606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe hemodynamic effects of quipazine, a serotonergic agent, were determined in pentobarbital‐anesthetized, open‐chest dogs administering the drug IV, either by bolus injection or by continuous infusion. Bolus injections of 0.1 and 1 mg/kg elicited transient increases in blood pressure, peripheral resistance, aortic flow, and stroke volume. Administration of 10 mg/kg decreased blood pressure, aortic flow, heart rate, cardiac contractility, and venous pressure, and increased stroke volume. Infusion of quipazine at a rate of 0.5 mg/kg/min for 30 min initially increased blood pressure and peripheral resistance and subsequently produced hypotension and decreased cardiac function. From the beginning of infusion, heart rate and venous pressure decreased, while stroke volume increased. Pretreatment with methysergide antagonized the hypotension and bradycardia, as well as the changes in venous pressure and stroke volume. It was concluded that quipazine elicits complex, dose‐related cardiovascular effects, some of which (hypotension, venodilatation, bradycardia) are mediated through methysergide‐sensitive central serotonin receptors. The arterial vasoconstriction produced by low doses of the drug was not mediated through these receptors and was probably the result of activation of a cardiogenic

ISSN:0272-4391    

DOI:10.1002/ddr.430040607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractSubcutaneous injection of amitraz (0.3–3.0 mg/kg) produced a dose‐dependent delay of gastrointestinal transit in conscious mice. This effect of amitraz was antagonized by α2‐adrenergic blocking agents, e.g., yohimbine, piperoxan, and tolazoline. Other adrenergic antagonists without α2‐blocking activity (thymoxamine, prazosin, phenoxybenzamine, and propranolol) did not reduce the depressant effect of amitraz on gastrointestinal transit at the dosages studied. Furthermore, this effect of amitraz was not altered by a dopaminergic antagonist (haloperidol), a serotonergic antagonist (methysergide), a histamine H1‐antagonist (chlorpheniramine), a histamine H2‐antagonist (cimetidine), cholinergic antagonists (atropine and hexamethonium), a GABAergic antagonist (bicuculline), and an opioid antagonist (naloxone). Pretreatment of mice with 6‐hydroxydopamine failed to antagonize the effect of amitraz. These results suggest that amitraz‐induced delay of gastrointestinal transit is mediated by postjunctional α2‐adrenergic receptors and appears not to involve the activation of β‐adrenergic, dopaminergic, serotonergic, histaminergic, cholinergic, GABAerg

ISSN:0272-4391    

DOI:10.1002/ddr.430040608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430040609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

ISSN:0272-4391    

DOI:10.1002/ddr.430040601

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY