Morphine increases 5-HT metabolism in the nucleus raphe magnus: an in vivo study in freely moving rats using 5-hydroxyindole electrochemical detection.

The purpose of this study was to evaluate in freely moving animals the effect of morphine on the 5-hydroxyindole oxidation current recorded in the nucleus raphe magnus (NRM) which is the origin of serotonergic control systems modulating the transmission of noxious inputs at the spinal level. A current recorded at 270-290 mV (peak 3), characteristic of 5-hydroxyindoleacetic acid (5-HIAA), was measured with treated multi-fiber carbon electrodes, using differential pulse (DPV) or differential normal pulse (DNPV) voltammetry. In control rats the amplitude of the peak remains constant for many hours. Morphine (10 mg/kg i.p.) caused a very significant increase which plateaued between 60 and 80 min (mean increase: 142 +/- 7% of control values); recovery was complete by about 3 h. Simultaneous injection of naloxone (1 mg/kg i.p.) completely abolished the effect of morphine. The peak 3 augmentation was still observed (151 +/- 5%) in rats pretreated with the xanthine oxidase inhibitor, allopurinol (12 mg/kg i.p.), but did not occur when animals were given an anaesthetic dose (450 mg/kg i.p.) of chloral hydrate. It is concluded that morphine clearly increases the metabolism of serotonin (5-HT) in the NRM, and one could speculate that the increase in 5-HIAA results from 5-HT release. Such a release could be due either to 5-HT terminals originating in the periaqueductal gray, or to somato-dendritic mechanisms. Thus the question remains as to the relationship between the activation of 5-HT metabolism in the NRM and previous neurochemical evidence for morphine-induced augmentation of 5-HT metabolism within the terminal area of serotonergic raphe-spinal pathways.