Inhibition by talipexole, a thiazolo-azepine derivative, of dopaminergic neurons in the ventral tegmental area.
A microiontophoretic study using rats anesthetized with chloral hydrate and immobilized with gallamine triethiodide was carried out to compare the effect of talipexole (B-HT 920 CL2:2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo [4,5-d]-azepine-dihydrochloride), a dopamine autoreceptor agonist, on dopaminergic neurons in the ventral tegmental area (VTA) to non-dopaminergic neurons in the VTA. VTA neurons were classified into two types according to the responses to antidromic stimulation of the nucleus accumbens (Acc): type I neurons with a long spike latency (8.69 +/- 0.24 msec) upon Acc stimulation and low spontaneous firing rate (6.80 +/- 1.34/sec), and type II neurons with a short latency (2.76 +/- 0.20 msec) and high spontaneous firing rate (26.77 +/- 7.05/sec), probably corresponding to dopaminergic and non-dopaminergic neurons, respectively. In type I neurons, microiontophoretic application of talipexole and dopamine inhibited antidromic spike generation elicited by Acc stimulation, and talipexole-induced inhibition was antagonized by domperidone (dopamine D-2 antagonist). In type II neurons, however, the antidromic spikes were not affected by either talipexole or dopamine. Furthermore, spontaneous firing was also inhibited by iontophoretically applied talipexole and dopamine in most type I neurons, but rarely affected by either drug. Inhibitory effects of talipexole were antagonized by domperidone. These results suggest that talipexole acts on dopamine D-2 receptors, thereby inhibiting the dopaminergic neurons in the VTA.
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
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Momiyama
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Sasa
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Takaori
D000818:Animals; D001381:Azepines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D007478:Iontophoresis; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
D001381:Azepines; D015259:Dopamine Agents; D004294:Domperidone; C024763:talipexole; D004298:Dopamine