Electrophysiological evidence for a non-opioid interaction between dynorphin and GABA in the substantia nigra of the rat.
Interactions between neuronal responses mediated by dynorphin A1-8 and GABA were investigated in the substantia nigra zona reticulata. Extracellular recordings and microiontophoresis were performed using five-barrel microelectrodes in chloral hydrate-anesthetized male rats. When iontophoresed alone, dynorphin A1-Q significantly inhibited the firing of 22% of the neurons tested. The inhibition was rapid in onset and recovery and was dose-dependent. In another 22% of the cells, iontophoretic dynorphin produced an increase in the baseline firing rate which was slow in both onset and offset; the remaining 56% were unaffected by dynorphin. When GABA and dynorphin A1-8 were applied in conjunction, the inhibitory action of GABA was attenuated in 61% of the cells; whereas, when dynorphin and GABA were ejected simultaneously onto the cells that were inhibited by dynorphin A1-8, the respective inhibitory effects of dynorphin and GABA appeared to be additive. The kappa antagonist, MR-2266, failed to block the ability of dynorphin A1-8 to attenuate the action of GABA. In addition, the non-opiate peptide des-tyr-dynorphin A2-17, produced effects similar to that of dynorphin A1-8. The role of dynorphin in the basal ganglia and its interaction with the other major transmitter in the substantia nigra zona reticulata, GABA, is discussed.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001575:Benzomorphans / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D004399:Dynorphins / Q000031:analogs & derivatives / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001575:Benzomorphans; D010446:Peptide Fragments; D011957:Receptors, Opioid; D009270:Naloxone; D012965:Sodium Chloride; D005680:gamma-Aminobutyric Acid; C027247:MR 2266; D004399:Dynorphins; C026770:dynorphin (1-8)