The effect of morphine on 5-hydroxytryptamine synthesis and metabolism in the striatum, and several discrete hypothalamic regions of the rat brain.

The effects of morphine on 5-hydroxytryptamine (5-HT) synthesis (accumulation of 5-hydroxytryptophan following inhibition of aromatic L-amino acid decarboxylase) and metabolism (concentration of 5-HT and its primary metabolite, 5-hydroxyindole-3-acetic acid [5-HIAA]) were determined in discrete nuclei of the rat brain using high performance liquid chromatography coupled with electrochemical detection (LCEC). Morphine (10 mg/kg, s.c.) increased 5-HT synthesis in the medial preoptic (MPO), suprachiasmatic (SCN) and arcuate (AN) nuclei as well as the striatum (ST) 1 hour following its administration. 5-HT synthesis in the median eminence (ME) was not affected at any time examined. A lower dose of morphine (5 mg/kg) also stimulated 5-HT synthesis in the AN. Although steady state concentrations of 5-HT were not greatly affected by morphine administration, the concentration of 5-HIAA in the AN, MPO, and ST increased following morphine (10 mg/kg, s.c., 1 hour). The increase in 5-HT synthesis observed in the MPO, SCN, AN, and ST 1 hour following morphine involved the activation of opiate receptors as administration of an opiate receptor antagonist, naloxone, blocked this effect. These results, indicate that morphine causes an increase in 5-HT synthesis and metabolism via an opiate receptor-mediated mechanism in the AN, MPO, SCN, and ST but not in the ME.