Microiontophoretic studies of the effects of D-1 and D-2 receptor agonists on type I caudate nucleus neurons: lack of synergistic interaction.
Several lines of evidence have suggested there may be a physiologically relevant form of synergistic interaction between D-1 and D-2 dopamine (DA) receptors located on postsynaptic neurons in the forebrain that receive a dopaminergic innervation. Because of the theoretical importance of such an interaction with respect to understanding the normal physiology of dopaminergic systems, we evaluated effects of D-1 and D-2 selective agonists, applied microiontophoretically, on the spontaneous electrical activity of a single, identifiable subpopulation of neurons within the caudate nucleus, the type I striatal neuron, in locally anesthetized, gallamine-paralyzed rats. It was observed that the D-2 receptor agonist quinpirole (QUIN) produced biphasic effects on cell firing rate. Low ejection currents significantly increased firing rate, while higher currents produced an inhibition. Similar effects were observed for the D-1 agonists SKF 38393; however, the overall excitations observed at low ejection currents were far less than those observed for QUIN. When these two agonists were applied concurrently, a simple additive effect (but not synergism) was always observed. The acute reduction of striatal levels of DA, by as much as 84% (with pretreatment with alpha-methyl-p-tyrosine, AMPT), did not alter the responsiveness of type I striatal neurons to the DA receptor agonists applied alone or in combination. These observed effects were not altered either by chloral hydrate anesthesia (in which glutamate-driven activity was studied) or by a more severe depletion of striatal DA levels (98% depletion produced by combined pretreatment with AMPT and reserpine).
Laboratory of Neurophysiology, Sinai Hospital, Detroit, Michigan.
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Shen
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Asdourian
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Chiodo
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects*; D002697:Chloral Hydrate; D015259:Dopamine Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004594:Electrophysiology; D004873:Ergolines / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007478:Iontophoresis; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019805:alpha-Methyltyrosine
D015259:Dopamine Agents; D004873:Ergolines; D005971:Glutamates; D008781:Methyltyrosines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D018698:Glutamic Acid; D002697:Chloral Hydrate; D019805:alpha-Methyltyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine