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.
Rivot
J P
JP
Unité de Recherches de Neurophysiologie Pharmacologique, I.N.S.E.R.M. U. 161, Paris, France.
Pointis
D
D
Besson
J M
JM
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004566:Electrodes; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity; D009270:Naloxone / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D012701:Serotonin; D009270:Naloxone; D000493:Allopurinol; D009020:Morphine; D010293:Pargyline; D014969:Xanthine Oxidase