摘要:

A previous study demonstrated the efficacy of the corticotropin-releasing hormone (CRH) receptor antagonist, α -helical CRH (9—41), in blocking the paradoxical sleep increase induced by stress. In the present study, this peptide was used to evaluate the involvement of the stress component of the sleep deprivation, in the paradoxical sleep rebound. Rats were subjected for 10 h to the classical water-tank sleep-deprivation technique and were given, every 2 h throughout the sleep deprivation period, intracerebroventricular injections of either 100 µg/5 µI of a-helical CRH (9—41) or vehicle alone. Continuous recordings showed that antagonist treatment decreased the PS rebound, but not the SWS rebound, following sleep deprivation. These findings suggest that, in the water-tank sleep deprivation method, stress, acting via CRH activation, is the main factor inducing the paradoxical sleep rebound.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

According to the generalized matching law the ratio of responses between two alternatives matches the ratio of reinforcers produced by these responses. In these experiments using concurrent variable-interval variable-interval schedules in pigeons, responding occurred more frequently on the key associated with the lower reinforcement density (undermatching) than would be predicted by perfect matching. Under control conditions, there was no bias toward responding on either key. Pentobarbital, methamphetamine, morphine and phencylidine all increased bias toward responding on the left key with the exception of one 10 mg/kg dose of pentobarbital that increased bias toward responding on the right key. Higher doses of methamphetamine and morphine, and most doses of phencyclidine increased matching, but high doses of pentobarbital further decreased matching. Morphine increased bias toward responding on the left key at much lower doses than those that affected matching, while phencyclidine increased matching at lower doses than those that increased bias. Pentobarbital produced small increases in response rates that were sometimes accompanied by small increases in key switching. All other drugs only decreased response rate and decreased the number of key switches. These data suggest that drugs disrupt responding under concurrent schedules both by increasing bias and by changing baseline matching functions.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study examined the effects on rat behaviour of antagonists acting at various sites on the N-methyl-D-aspartate (NMDA) receptor complex, i.e. the glutamate recognition site (CPP), ion channel (dizocilpine), glycine recognition site [(+)-HA-966] and the NR2B subunit-selective compound ifenprodil. Specifically, the effects of these agents were examined on working memory, assessed using the operant delayed match-to-position task (DMTP), and overt behaviour, assessed (a) in animals responding for food under a variable interval 20-s (VI20) schedule and (b) by spontaneous behaviour. Dizocilpine, CPP and (+)-HA-966 each reduced accuracy in the DMTP task independent of delay. At equivalent doses, changes in locomotor behaviour and VI20 responding were evident. In contrast, ifenprodil failed to impair accuracy in the DMTP task, even at doses that affected other performance measures and reduced VI20 responding. The relevance of these observations to neuroprotective and anticonvulsant doses of these compounds is considered.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A series of experiments was carried out to assess the effects of valproate (VAL) on the intake of ethanol by rats. In Experiment 1, the effects of VAL (150 and 200 mg/kg, i.p.) were assessed across 10 days. Compared with controls, the 200 mg/kg dose reliably reduced intake of ethanol while also reliably increasing intake of water. The 150 mg/kg dose did not reliably reduce the intake of ethanol across the initial days, but it did across later days. Neither dose affected the total intake of fluids. Similarly, 5 days of oral dosing with VAL (400 and 600 mg/kg) reliably reduced the intake of ethanol without affecting the intake of water. However, body weights were reduced by the oral doses across the procedure. In another procedure, VAL (200 mg/kg, i.p.) produced a mild conditioned taste aversion to a saccharin solution, suggesting that VAL may reduce intake of ethanol because it produces a general malaise. However, this dose of VAL enhanced the intoxicating effects of ethanol (2.0g/kg). Overall, the results are equivocal with respect to VAL as a potential medicine for treating alcohol misuse and alcoholism.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study aimed to investigate the effects of the opiate antagonist naloxone (10 mg/kg) on the action of a subeffective dose of chlordiazepoxide. C57BL/6 mice were tested for either anxiety, using an elevated plus maze, emotional memory in a passive avoidance paradigm or spatial memory in a radial maze. In the elevated plus maze, chlordiazepoxide 2.5 mg/kg was ineffectiveper sebut, when combined with naloxone, it increased the proportion of open-arm entries, as did a higher dose of chlordiazepoxide (5 mg/kg). Closed-arm entries were increased with chlordiazepoxide (2.5 mg/kg) injected alone but naloxone, alone or combined with chlordiazepoxide, did not modify this measure. In the passive avoidance test, chlordiazepoxide 2.5 mg/kg decreased the latency to enter a compartment associated with an electric foot-shock, while a dose of 1.25 mg/kg, alone or in combination with naloxone, was ineffective. Finally, in the radial arm maze, chlordiazepoxide (5 mg/kg) induced amnesia. However, a dose of 2.5 mg/kg, alone or with naloxone, had no effect on learning. Naloxone elicited no intrinsic action in any of these behavioural models. It can be concluded that naloxone potentiates the anxiolytic but not the amnestic action of chlordiazepoxide.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using a wide range of receptor subtype-selective agonists and antagonists. Only the muscarinic receptor antagonist scopolamine generalized fully to clozapine (> 80%). Partial generalization (defined here as 40% maximal generalization) was seen with the Di receptor antagonist SCH 23390 (43% maximal generalization), the α1-adrenoceptor antagonist prazosin (67%) and the α2-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced<25% maximal generalization, including the a2-adrenoceptor antagonist yohimbine (24%), the histamine H1receptor antagonist mepyramine (21%), the D2antagonist typical neuroleptic haloperidol (23%), the D4receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-lA (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2Areceptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2Creceptor antagonists SB 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D1receptor antagonist SCH 23390, or by the 5-HT1Areceptor antagonist WAY 100635, when given concomitantly with clozapine. Although the results suggest that muscarinic antagonism plays a major role in the clozapine cue, the results have to be considered in the light of the full generalization to clozapine seen with various antipsychotic agents which have very low affinity for muscarinic receptors, including zotepine, quetiapine, JL13 and PNU 96415 (a finding replicated in rats from the same breeding colony as those which generalized to scopolamine). Thus, generalization to clozapine for antipsychotics with multiple affinities but with low muscarinic affinity is probably mediated by additive or perhaps supra-additive actions at other receptors, although extensive studies with various combinations of drug mixtures are required to validate this hypothesis.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A neural network model of classical conditioning is applied to the description of some aspects of the psychopharmacology of latent inhibition (LI). According to the model, LI is manifested because preexposure of the conditioned stimulus (CS) reduces Novelty, defined as proportional to the sum of the mismatches between predicted and observed events, thereby reducing attention to the CS and retarding conditioning. In the framework of the model, it is assumed that indirect dopaminergic (DA) agonists (e.g. amphetamine and nicotine) increase, and DA receptor antagonists (e.g. haloperidol and et-flupenthixol) decrease, the effect of Novelty on attention. Computer simulations demonstrate that, under these assumptions, the model correctly describes: (1) the impairment of LI by amphetamine when a strong unconditioned stimulus (US) is used, (2) the impairment of LI by amphetamine when a nonsalient CS is used, (3) the impairment of LI by amphetamine administration when a short CS is used, (4) the facilitation of LI by a-flupenthixol when a weak US is used, (5) the facilitation of LI by haloperidol when a nonsalient CS is used, (6) the facilitation of LI by haloperidol with a strong US, and (7) the facilitation of LI by haloperidol with extended conditioning.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The interaction with monoamine oxidase A (MAO-A) and B has been shown to be sensitive to the absolute configuration of molecules. Therefore, the aim of this study was to compare the effects of the racemic pirlindole (a selective and reversible MAO-A inhibitor) and its two enantiomers using biochemical techniques (in vitroandex vivodetermination of rat brain MAO-A and MAO-B activity) and behavioural models (forced swimming test and reserpine-induced hypothermia and palpebral ptosis test).In vitro, the MAO-A IC50of (±)-pirlindole, R-(—)-pirlindole and S-(+)-pirlindole were 0.24, 0.43 and 0.18 (j,M, respectively.Ex vivo, their ID50were 24.4, 37.8 and 18.7 mg/kg i.p. The differences between the three compounds were not significant, with a ratio between the two enantiomers [R-(—)/S-(+)] of 2.2in vitroand 2.0ex vivo. MAO-B was only slightly inhibited. In the forced swimming test and the reserpine-induced hypothermia and ptosis model, the three compounds had an antidepressant profile. In the forced swimming test, the minimal effective dose ratio between the R-(-) and the S-(+) was again around 2.0. The behavioural observations were thus clearly in accordance with the biochemical data.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID