Low Dose Naloxone Attenuates the Pruritic but Not Anorectic Response to Rimonabant in Male Rats

Rationale: Previous research suggests that the acute anorectic effect of cannabinoid CB1 receptor antagonist/inverse agonists may be secondary to response competition from the compulsive scratching and grooming syndrome characteristic of these agents.

Objectives: As the pruritic effect of rimonabant can be attenuated by the opioid receptor antagonist naloxone, these studies test the prediction that naloxone co-treatment should prevent acute rimonabant anorexia.

Methods: Two experiments comprehensively profiled the behavioural effects of an anorectic dose of rimonabant (1.5 mg/kg) in the absence or presence of naloxone (experiment 1: 0.01 or 0.1 mg/kg; experiment 2: 0.05 mg/kg).

Results: In both experiments, rimonabant not only significantly suppressed food intake and time spent eating but also induced compulsive scratching and grooming. In experiment 1, although the lower dose of naloxone seemed to weakly attenuate the effects of rimonabant both on ingestive and compulsive behaviours, the higher dose more strongly suppressed the compulsive elements but did not significantly affect the anorectic response. The results of experiment 2 showed that naloxone at a dose which markedly attenuated rimonabant-induced grooming and scratching did not alter the effects of the compound on food intake or time spent feeding. The apparent independence of the ingestive and compulsive effects of rimonabant was confirmed by the observation that despite a 'normalising' effect of naloxone co-treatment on behavioural structure (BSS), the opioid antagonist did not impact the suppressant effect of rimonabant on peak feeding.

Conclusion: The acute anorectic response to rimonabant would not appear to be secondary to compulsive scratching and grooming.