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

V. Deroche-Gamonet, M. Le Moal, P. Piazza, P. Soubrié
Psychopharmacology. 2001-07-20; 157(3): 254-259
DOI: 10.1007/s002130100804

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1. Psychopharmacology (Berl). 2001 Sep;157(3):254-9.

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

Deroche-Gamonet V(1), Le Moal M, Piazza PV, Soubrié P.

Author information:
(1)Laboratoire de Psychobiologie des Comportements Adaptatifs, Domaine de
Carreire, Rue Camille Saint-Saëns, 33077 Bordeaux, France.

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.

DOI: 10.1007/s002130100804
PMID: 11605080 [Indexed for MEDLINE]


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