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

Rationale: The endogenous cannabinoid system is thought to play a role in r einforcement processes. Objectives: We tested the effects of five doses of the cannabinoid receptor 1 (CB1) antagonist SR141716 [0, 0.3, 1, 3 and 10 m g/kg, intraperitoneal (IP)] on intracranial self-stimulation at the level o f the median forebrain bundle (MFB). Self-stimulation was assessed 30 min a nd 210 min after SR141716 administration. We compared the effect of SR14171 6 with the effect of a decrease in the magnitude of stimulation (-100 muA) 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 (RMa x) were used as the parameters to characterize the rate-frequency functions . Results: SR141716 decreased the sensitivity to the electrical brain stimu lation. 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 s ignificant decrease in sensitivity to electrical stimulation, as shown by a n elevation in the M50 value. RMax showed a tendency to decrease with incre asing doses. At 210 min after administration, 3 and 10 mg/kg SR141716 maint ained their decreasing effect on the sensitivity to the stimulation as show n by the significant increase of the M50, however, the maximal response was restored to the basal value. A decrease in self-stimulation intensity prod uced an effect comparable to the one observed 30 min after either 3 or 10 m g/kg, SR141716, while cocaine (5 and 10 mg/kg) produced the opposite effect . Neither condition affected the rate-frequency curve measured 3 h later. C onclusions: In accordance with recent observations, these experiments sugge st 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 implic ating the reinforcing system.