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Vol. 290, Issue 3, 1307-1315, September 1999

Modulation of Neurotransmitter Release in the Basal Ganglia of the Rat Brain by Dynorphin Peptides1

Zhi-Bing You , Mario Herrera-Marschitz and Lars Terenius

Departments of Physiology and Pharmacology (Z.-B.Y., M.H-M.) and Clinical Neuroscience (Z.-B.Y., L.T.), Karolinska Institutet, Stockholm, Sweden

Microinjection studies have found that although dynorphin peptides decrease dopamine release in the rat basal ganglia, the nonselective opiate antagonist naloxone produces the opposite effect. To investigate the contribution of the dynorphin pathways to a tonic modulation of dopamine release, a microdialysis study was undertaken, with probes implanted in the substantia nigra and the ipsilateral neostriatum. Perfusion of the substantia nigra with the nonselective antagonist naltrexone (NTX; 1-10 µM), the selective kappa -opoid receptor antagonist, nor-binaltorphimine (nor-BNI; 1-10 µM), and the selective µ-opioid receptor antagonist, D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; 1-10 µM) produced an increase in dopamine release, both in substantia nigra and neostriatum. nor-BNI also produced an increase in dynorphin B release, and a similar effect was observed with the higher concentration of NTX (10 µM). At the higher concentration of NTX and CTOP, an increase in glutamate release was also observed. Perfusion of the neostriatum 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 release. The kappa -opioid agonist U-50,488H (10 µM) induced a decrease in dopamine levels, both in the substantia nigra and neostriatum, and a paradoxical increase in striatal aspartate levels. Finally, systemic administration of NTX (4 mg/kg s.c.) in awake animals significantly increased striatal dopamine levels. The results suggest that opioid peptides, either dynorphins acting on kappa -opioid receptors or enkephalins acting on µ-opioid receptors, exert tonic inhibition on dopamine and dynorphin B release in both substantia nigra and neostriatum.

0022-3565/99/2903-1307$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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