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Abstract: In the present study, sexual behavior of male rats was assessed following prolonged treatment with the CB1 receptor agonist, HU-210 (0.1mg/mg/day for 10 days) under conditions of drug maintenance, spontaneous withdrawal and precipitated withdrawal (induced via administration of the CB1 receptor antagonist AM251; 1mg/kg). Following subchronic cannabinoid treatment, sexual activity in male rats was impaired under both the drug maintenance and spontaneous withdrawal conditions, as revealed by a reduction in frequency of both intromissions and ejaculations. Notably, the induction of precipitated drug withdrawal reversed the negative effects of subchronic HU-210 treatment on sexual activity as seen by a reversal of the suppression of ejaculations. These data illustrate that, contrary to expectations, the impairments in male sexual activity following protracted cannabinoid administration are not due to drug withdrawal, per se, but are likely mediated by neuroadaptive changes provoked by repeated drug exposure. [Copyright &y& Elsevier]

Abstract: Research has shown that enhancement of cannabinoid CB1 receptor activity elicits an antidepressant-like response in the forced swim test (FST); however, the effects of chronic administration of cannabinoid agents in the FST are not well characterized. In Experiment 1, the CB1 receptor agonist HU-210 (0.1 mg/kg) was administered for 10 days to male rats, following which animals were exposed to the FST. In Experiment 2, the same protocol was utilized; however, prior to the FST animals were co-treated with either prazosin (1 mg/kg; an α1-adrenoreceptor antagonist) or propranolol (2.5 mg/kg; a β-adrenoreceptor antagonist). In Experiment 3, the same protocol was employed in both male and female rats, and the role of drug withdrawal was examined by administration of the CB1 receptor antagonist AM251 (1 mg/kg) prior to the FST. Experiment 1 revealed that HU-210 administration evoked a reduction in immobility and increase in struggling that was identical to that produced by the antidepressant desipramine (10 mg/kg). Experiment 2 revealed that this effect was attenuated by both α- and β-adrenoreceptor antagonists, suggesting noradrenergic involvement in this antidepressant-like profile. Experiment 3 demonstrated that HU-210 administration produced an antidepressant response in both males and females, which was attenuated by the induction of precipitated withdrawal. These results show that protracted administration of a CB1 receptor agonist produces an antidepressant-like response in the FST in both sexes, which appears to involve the noradrenergic system. [Copyright &y& Elsevier]