Highly potent inhibitory effects of 5-HT3 receptor antagonist, GR38032F, on non-opioid defeat analgesia in male mice.

Behavioural and pharmacological evidence indicates that non-opioid analgesia in defeated male mice is initiated by anxiety and that serotongergic (5-HT) substrates are implicated. In the present study, the effects of the novel putative 5-HT3 anxiolytic, GR38032F, on this form of adaptive inhibition of pain have been examined. The results showed that defeat analgesia was totally inhibited by 1 microgram/kg-1 mg/kg of GR38032F, with partial inhibition evident over the dose range of 0.0001-0.1 microgram/kg and loss of efficacy at smaller doses. These highly potent effects of GR38032F are consistent with its anxiolytic profile in animal models and cannot be accounted for by indirect actions on basal nociception. These findings point to a potentially important modulatory role for 5-HT3 receptor mechanisms in defeat analgesia and, more generally, provide further evidence for the involvement of 5-HT in the mediation of non-opioid forms of environmentally-induced antinociception.