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Titolo:
Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands
Autore:
Goudie, AJ; Smith, JA; Taylor, A; Taylor, MAI; Tricklebank, MD;
Indirizzi:
Univ Liverpool, Dept Psychol, Liverpool L69 7ZA, Merseyside, England Univ Liverpool Liverpool Merseyside England L69 7ZA , Merseyside, England Novartis Pharma AG, Nervous Syst Res, Basel, Switzerland Novartis Pharma AG Basel Switzerland rvous Syst Res, Basel, Switzerland
Titolo Testata:
BEHAVIOURAL PHARMACOLOGY
fascicolo: 8, volume: 9, anno: 1998,
pagine: 699 - 710
SICI:
0955-8810(199812)9:8<699:DSPOTA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIPSYCHOTIC-DRUGS; 5-HT1A RECEPTORS; ALPHA(2)-ADRENOCEPTOR ANTAGONISM; BEHAVIORAL PHARMACOLOGY; TYPICAL NEUROLEPTICS; DOPAMINE D-1; SB 200646A; PROFILE; SCHIZOPHRENIA; AGONIST;
Keywords:
clozapine; drug discrimination; drug mixtures; mode of action; rats; scopolamine; neuroleptics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Goudie, AJ Univ69iverpool, Dept Psychol, Eleanor Rathbone Bldg,Bedford St,Liverpool L Univ Liverpool Eleanor Rathbone Bldg,Bedford St Liverpool Merseyside England L69 7ZA
Citazione:
A.J. Goudie et al., "Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands", BEHAV PHARM, 9(8), 1998, pp. 699-710

Abstract

The interoceptive stimulus induced by clozapine (5 mg/kg, i.p.) has been characterized in an operant drug discrimination procedure in the rat using aaide 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 D-1 receptor antagonist SCH 23390 (43% maximal generalization), the alpha(1)-adrenoceptor antagonist prazosin (67%) and the alpha(2)-adrenoceptor antagonist methoxyidazoxan (42%). All other specific agents tested induced <25% maximal generalization, including the alpha(2)-adrenoceptor antagonist yohimbine (24%), the histamine H-1 receptor antagonist mepyramine (21%), the D-2 antagonist typical neuroleptic haloperidol (23%), the D-4 receptor antagonist L-745,870 (14%), the 5-hydroxytryptamine-1A (5-HT1A) receptor agonist S-14506 (8%), the 5-HT2A receptor antagonists ketanserin (0%) and M100907 (12%), the 5-HT2B/2C receptor antagonists SE 200646A (8%) and SDZ SER 082 (6%), and the 5-HT3 receptor antagonist ondansetron (0%). The clozapine discriminative stimulus was not blocked by the dopamine D-1 receptor antagonist SCH 23390, or by the 5-HT1A receptor 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. Behav Pharmacol 1998; 9:699-710 (C) 1998 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 20:06:31