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Central mediation and differential blockade by cannabinergics of the discriminative stimulus effects of the cannabinoid CB receptor antagonist rimonabant in rats.
- Source :
-
Psychopharmacology . Aug2011, Vol. 216 Issue 3, p355-365. 11p. - Publication Year :
- 2011
-
Abstract
- Rationale: Discovery of an endocannabinoid signaling system launched the development of the blocker rimonabant, a cannabinoid CB1 receptor (CBR) antagonist/inverse agonist. Due to untoward effects, this medication was withdrawn and efforts have been directed towards discovering chemicals with more benign profiles. Objective: This study aims to comparatively evaluate new ligands using a rimonabant discriminated drinking aversion procedure. Methods: Rats discriminated between rimonabant (5.6 mg/kg) and vehicle. The 30 min saccharin (0.1%) drinking after rimonabant pretreatment was followed by injection of lithium chloride (120 mg/kg) in the experimental animals. After vehicle pretreatment, experimental animals were given i.p. NaCl (10 ml/kg). Postdrinking treatment for controls was NaCl, irrespective of pretreatment condition (rimonabant or vehicle). Results: The centrally acting neutral CBR antagonist AM4113, but not the limited brain penetrating CBR neutral antagonist AM6545, substituted for rimonabant. The CBR agonists THC (1-10 mg/kg), AM1346 (1-10 mg/kg) did not substitute. The rimonabant-induced conditioned suppression of saccharin drinking was attenuated when CBR agonists AM5983 (0.01-1 mg/kg) and THC (10 mg/kg), but not the CBR agonist AM1346 (0.1-18 mg/kg), were combined with rimonabant (5.6 mg/kg). By varying the injection-to-test interval, we gauged the relative duration of the cueing effects of rimonabant, and the in vivo functional half-life was estimated to be approximately 1.5 h. Conclusion: A neutral CBR antagonist (AM4113) produced cueing effects similar to those of rimonabant and generalization likely was centrally mediated. The functional cueing effects of rimonabant are relatively short-acting, pharmacologically selective, and differentially blocked by cannabinergics. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 216
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 62519120
- Full Text :
- https://doi.org/10.1007/s00213-011-2226-3