EFFECT OF MORPHINE ON DYNORPHIN-B AND GABA RELEASE IN THE BASAL GANGLIA OF RATS

In vivo microdialysis was used to study the effects of systemic, as we ll as intracerebral administration of morphine and naloxone on dynorph in B release in neostriatum and substantia nigra of rats. The release of dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (Glu) and aspartate (Asp) was also investigated. Systemic injection of morphine (1 mg/kg s.c.) induced long-lasting increases in extracellular dynorph in B and GABA levels in the substantia nigra, whereas DA, Glu and Asp levels, measured in the same region, were not significantly affected. No effect on striatal neurotransmitter levels was observed following s ystemic morphine administration. Local perfusion of the substantia nig ra with morphine (100 mu M) through the microdialysis probe also incre ased nigral dynorphin B and GABA levels. Perfusion of the neostriatum with morphine (100 mu M) significantly increased GABA and dynorphin B levels in the ipsilateral substantia nigra, but no effect was observed locally. Naloxone blocked the effect of systemic morphine administrat ion on nigral dynorphin B and GABA release, already at a dose of 0.2 m g/kg s.c. Naloxone alone, given either systemically (0.2-4 mg/kg s.c.) or intracerebrally (1-100 mu M), did not affect dynorphin B or amino acid levels, either in neostriatum or in substantia nigra. However, na loxone produced a concentration-dependent increase in DA levels. The p resent results indicate that systemic morphine administration stimulat es the release of dynorphin B in the substantia nigra, probably by act ivating the mu-subtype of opioid receptor, since the effect of morphin e on nigral dynorphin B and GABA was antagonized by a low dose of nalo xone. The increase in extracellular DA levels produced by high concent rations of naloxone, both in neostriatum and substantia nigra, indicat es a disinhibitory effect of this drug on DA release, probably via a n on-mu subtype of opioid receptors located on nigro-striatal DA neurone s.