A mesolimbic neuronal loop of analgesia: I. Activation by morphine of a serotonergic pathway from periaqueductal gray to nucleus accumbens.

A cerebral neuronal circuit implicated in morphine analgesia was studied in rabbits equipped with chronic intracerebral cannulae directed to periaqueductal grey (PAG) and to bilateral nuclei accumbens. Microinjection of morphine (10 micrograms) into PAG elicited a marked analgesic effect as measured by the latency of a radiant heat induced head-withdrawal reaction. This effect was dose-dependently attenuated by cinanserin, a serotonin (5-HT) blocker, and potentiated by 5-hydroxytryptophan (5-HTP), the direct precursor for 5-HT, administered into the nucleus accumbens. A significant analgesia was also shown when 5-HT (10 micrograms) was injected directly into the nucleus accumbens. The results suggest that morphine acting on PAG seems to activate an ascending serotonergic pathway and, by releasing 5-HT in nucleus accumbens, to exert an analgesic effect.