5-HT mediation of the antiaversive effect of isamoltane injected into the dorsal periaqueductal grey.

A previous study from this laboratory reported an antiaversive effect of the beta-adrenoceptor blocker propranolol microinjected into the dorsal periaqueductal grey (DPAG) of the rat, that was antagonized by the 5-HT(2) receptor blocker ritanserin. The present results show that microinjection into the DPAG of isamoltane (4-32nmol) a beta-blocking agent that binds to 5-HT(1B) receptors more selectively than propranolol, raised the threshold of aversive electrical stimulation of the rat DPAG in a dose-dependent manner. The antiaversive effect of 8nmol of isamoltane was antagonized by pretreatment with ritanserin (10nmol), as well as by the more selective 5-HT(2) receptor blocker ketanserin (10nmol). Therefore, the antiaversive effect of beta-adrenoceptor/5-HT(1B) receptor antagonists injected into the DPAG is likely to be mediated by endogenous 5-HT, through activation of 5-HT(2) receptors.