Naloxone reversible reduction in brain monoamine synthesis following sciatic nerve stimulation

Summary

Brain monoaminergic neurons seem to be influenced by endogenous opioid systems as judged from largely indirect evidence. In an attempt to more directly study this interaction, we have analyzed the effect of sciatic nerve stimulation (rectangular pulses, frequency 3 Hz, pulse duration 0.2 msec, current intensity 6–20 times muscle twitch threshold) on thein vivo rate of tyrosine- and tryptophanhydroxylation, respectively, in the rat brain. This stimulation procedure has previously been shown to evoke naloxone reversible pain threshold elevation and a longlasting blood pressure reduction in rats, with maximum reached about 1.5 h after stimulation. The formation of DOPA and 5-HTP in various parts of the central nervous system during 30 min after inhibition of L-amino-acid-decarboxylase by NSD 1015 was measured. Two hours after the sciatic nerve stimulation procedure a significant decrease in DOPA formation was obtained in the cerebral cortex and in the spinal cord. This effect was reversed by pretreatment with a high dose of naloxone (15 mg/kg s.c, 10 min before stimulation). A reduction in 5-HTP formation was also obtained in the cerebral cortex, with a concomitant reduction in tryptophan concentration. These effects appeared to be antagonized by naloxone treatment. In the spinal cord there was no change in the 5-HTP accumulation after stimulation, but an increase after stimulation plus naloxone pretreatment was obtained. These data infer that the activity of some central monoamine systems, such as the NA pathways originating in locus coeruleus can be reduced by physiological activation of endogenous opioid systems. This effect of the acupuncture like stimulation procedure may be related to clinically reported actions of acupuncture stimulation, which apart from pain relief include, for example, antagonism of heroin abstinence symptoms.