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SR141716, a CB1 receptor antagonist, decreases the sensitivity to the reinforcing effects of electrical brain stimulation in rats.

Abstract：

RATIONALE:The endogenous cannabinoid system is thought to play a role in reinforcement processes. OBJECTIVES:We tested the effects of five doses of the cannabinoid receptor 1 (CB1) antagonist SR141716 [0, 0.3, 1, 3 and 10 mg/kg intraperitoneal (IP)] on intracranial self-stimulation at the level of the median forebrain bundle (MFB). Self-stimulation was assessed 30 min and 210 min after SR141716 administration. We compared the effect of SR141716 with the effect of a decrease in the magnitude of stimulation (-100 microA) and the effects of a cocaine injection (1, 5 and 10 mg/kg IP). METHODS:a protocol of rate-frequency curve for self-stimulation was applied. Two rate-frequency curves were established daily, 3 h apart. The frequency required to produce half-maximal performance (M50) and the maximal performance (RMax) were used as the parameters to characterize the rate-frequency functions. RESULTS:SR141716 decreased the sensitivity to the electrical brain stimulation. SR141716 induced a shift to the right of the rate-frequency curve. This effect depended on the dose administered and the time after injection. Thirty minutes after the injection, 1, 3 and 10 mg/kg SR141716 induced a significant decrease in sensitivity to electrical stimulation, as shown by an elevation in the M50 value. RMax showed a tendency to decrease with increasing doses. At 210 min after administration, 3 and 10 mg/kg SR141716 maintained their decreasing effect on the sensitivity to the stimulation as shown by the significant increase of the M50, however, the maximal response was restored to the basal value. A decrease in self-stimulation intensity produced an effect comparable to the one observed 30 min after either 3 or 10 mg/kg SR141716, while cocaine (5 and 10 mg/kg) produced the opposite effect. Neither condition affected the rate-frequency curve measured 3 h later. CONCLUSIONS:In accordance with recent observations, these experiments suggest that the endogenous cannabinoid system facilitates the perception or the effects of positive reinforcers. They also suggest that this neurochemical system could be a target of interest for treating psychopathologies implicating the reinforcing system.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Deroche-Gamonet V,Le Moal M,Piazza PV,Soubrié P

doi

10.1007/s002130100804

subject

Has Abstract

pub_date

2001-09-01 00:00:00

pages

254-9

issue

eissn

0033-3158

issn

1432-2072

journal_volume

157

pub_type

杂志文章

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SR141716, a CB1 receptor antagonist, decreases the sensitivity to the reinforcing effects of electrical brain stimulation in rats.