INVOLVEMENT OF THE PERIAQUEDUCTAL GREY MATTER AND SPINAL 5‐HYDROXYTRYPTAMINERGIC PATHWAYS IN MORPHINE ANALGESIA: EFFECTS OF LESIONS AND 5‐HYDROXYTRYPTAMINE DEPLETION

Abstract

1 Electrolytic lesions of the periaqueductal grey matter (PAG) were made in rats. The analgesia produced by intraperitoneal injection of morphine (10 and 20mg/kg), tested by the tail flick and hot plate methods, was substantially reduced in the lesioned rats. Baseline pain thresholds were unaffected by the lesions. 2 The lesion effects were not due to damage to the dorsal raphe nucleus. The extent of histologically determined damage to the dorsal raphe and the resulting decrease in striatal 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations did not correlate with the reduction in morphine analgesia produced by the lesion. Furthermore, microinjections of 5, 6-diHYDROXYTRYPTAMINE (5,6-DHT) into the dorsal raphe nucleus produced a similar fall in 5-HIAA levels but had no effect on morphine analgesia. 3 Selective destruction of the periventricular catecholamine system produced by microinjection of 6-hydroxydopamine (6-OHDA) caused a slight decrease in morphine analgesia, thus raising the possibility that catecholamines may be involved in the action of morphine in the PAG. 4 5,7-Dihydroxytryptamine-induced lesions of the spinal cord 5-hydroxytryptaminergic pathways reduced cord 5-HT concentration by 70% and markedly attenuated morphine analgesia as determined by the tail flick test. 5 These experiments provide additional evidence that the PAG is a major site of action of opiates in producing analgesia. Furthermore, they have demonstrated the probable involvement of spinal 5-hydroxytryptaminergic pathways in the mediation of opiate analgesic effects.