Non-selective opioid receptor antagonism of the antidepressant-like effect of venlafaxine in the forced swimming test in mice.

The opioid system has been implicated in mood disorders as well as in the mechanism of action of antidepressants. Since the opioid component in venlafaxine (VLX) is still a matter of discussion, we investigated the role of opioid receptors in the antidepressant-like effect of VLX in the forced swimming test in mice. The non-selective opiate antagonist naloxone at high dose (2 mg/kg, s.c.) antagonized the effect of VLX. In contrast, beta-funaltrexamine (40 mg/kg, s.c.), which preferentially blocks mu(1)/mu(2) opioid receptors, naloxonazine (35 mg/kg, s.c.), a selective mu(1) opioid antagonist, naltrindole (10 mg/kg, s.c.), a selective delta opioid antagonist, and Nor-binaltorphimine (10 mg/kg, s.c.), which selectively blocks kappa-opioid receptors, were all ineffective. Thus, although apparently mediated by the opioid system, the behavioural effect of VLX does not involve specific opioid receptors.