Suppressing effect of rimonabant on the operant self-administration of a chocolate-flavoured beverage in rats

Paola Maccioni, Daniela Pes, Alessandro Orrù, Gian Luigi Gessa, Giancarlo Colombo, Mauro A.M. Carai. C.N.R. Institute of Neuroscience, Cagliari, Italy.

Previous work indicated that the CB1 cannabinoid receptor antagonist, rimonabant, selectively suppressed the intake of a highly palatable food, such as a chocolate-flavoured beverage (chocolate), in rats concurrently exposed in their homecage to chocolate, regular food pellets, and water (Gessa et al., 2006). The present study extended the characterization of this effect to an operant procedure of self-administration of chocolate.

Male Wistar rats (approximately 300 g), were trained to lever-press on a fixed ratio 10 (FR10) schedule to gain 3-s access to chocolate [5% (w/v) Nesquik® in water] in daily 20-min sessions. Rats rapidly acquired and maintained this behaviour, averaging 800-900 responses and self-administering approximately 45-50 ml/kg chocolate in each session. Subsequently, the effect of rimonabant (0, 1, 3, and 5.6 mg kg-1, i.p.) on responding for chocolate was determined. Two schedules of reinforcement were used: FR10 (which measures chocolate’s reinforcing properties) and progressive ratio (PR) (where the response requirement was increased progressively over the session; it measures chocolate’s motivational properties). A third experiment assessed the effect of rimonabant on extinction responding for chocolate (on the test session, chocolate was not presented, and non-reinforced (or extinction) responding, defined as the total number of responses emitted by each rat, was recorded; another measure of chocolate’s motivational properties).

Pretreatment with rimonabant resulted in a dose-dependent suppression of responding for chocolate on the FR10 schedule; specifically, responding in 1, 3, and 5.6 mg kg-1 rimonabant-treated rats was approximately 25%, 50%, and 75% lower, respectively, than in vehicle-treated rats [F(3,47)=26.18, P<0.0001]. Pretreatment with rimonabant resulted in a dose-dependent suppression in responding for chocolate on the PR schedule, as breakpoint for chocolate (defined as the lowest response requirement not achieved by the rat) in 1, 3, and 5.6 mg kg-1 rimonabant-treated rats was approximately 15%, 20%, and 65% lower, respectively, than in vehicle-treated rats [F(3,39)=6.37, P<0.005]. Pretreatment with rimonabant resulted in a dose-dependent suppression of extinction responding for chocolate, as values of extinction responding in 1, 3, and 5.6 mg kg-1 rimonabant-treated rats were approximately 40%, 55%, and 70% lower, respectively, than in vehicle-treated rats [F(3,47)=6.07, P<0.005].

These results constitute (a) further experimental evidence in support of the hypothesis that the CB1 cannabinoid receptor is part of the neural substrate mediating the reinforcing and motivational properties of highly palatable foods (see Carai et al., 2006; Cota et al., 2006), and (b) confirmation of the anorectic properties of rimonabant (see Carai et al., 2006; Halford, 2006).

Carai et al. (2006) CNS Drug Rev 12: 91-99

Cota et al. (2006) Brain Res. Rev 51: 85-107

Gessa et al. (2006) Psychopharmacology 185: 248-254

Halford (2006) Curr Opin Investig Drugs 7: 312-318.