Modulation of neurotransmitter release in the basal ganglia of the rat brain by dynorphin peptides

Microinjection studies have found that although dynorphin peptides decrease dopamine release in the rat basal ganglia, the nonselective opiate antagon ist naloxone produces the opposite effect. To investigate the contribution of the dynorphin pathways to a tonic modulation of dopamine release, a micr odialysis study was undertaken, with probes implanted in the substantia nig ra and the ipsilateral neostriatum. Perfusion of the substantia nigra with the nonselective antagonist naltrexone (NTX; 1-10 mu M), the selective kapp a-opoid receptor antagonist, nor-binaltorphimine (nor-BNI; 1-10 mu M), and the selective mu-opioid receptor antagonist, D-Pen-Cys-Tyr-o-Trp-Orn-Thr-Pe n-Thr-NH2 (CTOP; 1-10 mu M) produced an increase in dopamine release, both in substantia nigra and neostriatum. nor-BNI also produced an increase in d ynorphin B release, End a similar effect was observed with the higher conce ntration of NTX (10 mu M). At the higher concentration of NTX and CTOP, an increase in glutamate release was also observed. Perfusion of the neostriat um with NTX, nor-BNI, or CTOP increased striatal dopamine, and dynorphin B release and increased dynorphin B in the ipsilateral substantia nigra. NTX and CTOP, but not nor-BNI, increased striatal glutamate and aspartate relea se. The kappa-opioid agonist U-50,488H (10 mu M) induced a decrease in dopa mine levels, both in the substantia nigra and neostriatum, and a paradoxica l increase in striatal aspartate levels. Finally, systemic administration o f NTX (4 mg/kg s.c.) in awake animals significantly increased striatal dopa mine levels. The results suggest that opioid peptides, either dynorphins ac ting on kappa-opioid receptors or enkephalins acting on mu-opioid receptors , exert tonic inhibition on dopamine and dynorphin B release in both substa ntia nigra and neostriatum.