Opiate-receptor mediated changes in monoamine synthesis in rat brain.

Abstract

Abstract The effects of morphine, β-endorphin, naloxone and naltrexone on the rate of tyrosine and tryptophan hydroxylation were investigated in vivo by measuring the accumulation of dopa and 5-hydroxytryptophan (5-HTP) in different brain regions of rats after inhibition of the aromatic L-amino acid decarboxylase. The cerebral concentrations of tyrosine and tryptophan were also measured. Morphine (3–30 mg kg−1) increased the accumulation of dopa dose-dependently (25–50%) in the dopamine-rich areas (limbic forebrain and corpus striatum). In the noradrenaline-predominant parts of the brain (containing hemispheres, diencephalon and lower brain stem) only the highest dose of morphine (30 mg kg−1) significantly increased dopa formation (47%). Similarly to morphine, intracerebroventricularly injected β-endorphin (5–10 βg per rat) increased the formation of dopa. This increase was doubled in limbic forebrain, corpus striatum and cerebral hemispheres. Doses of 10 to 20 μg of β-endorphin were needed to increase dopa accumulation in the diencephalon and the lower brain stem. Naloxone antagonized the β-endorphin-induced increases in dopa. But naloxone and naltrexone (10–100 mg kg−1) decreased the dopa formation in the dopamine-rich areas (about 20–25 %) but not in the noradrenaline-predominant areas. Morphine (30 mg kg−1) and β-endorphin (5 μg per rat) increased the accumulation of 5-HTP whereas naloxone and naltrexone (10 mg kg−1) tended to decrease its formation. Morphine and β-endorphine increased the concentrations of tyrosine and tryptophan, and naloxone decreased the cerebral tryptophan concentration. These results show that the effects of a narcotic agonist (morphine) and of pure narcotic antagonists (naloxone and naltrexone) on the synthesis of dopamine and 5-HT are opposite to each other. Furthermore, the effects of β-endorphine on brain monoamine synthesis are remarkably similar to those of morphine. Thus, it is probable that opiate receptors and their endogenous ligands are involved in the regulation of dopamine and 5-HT synthesis.