Effects of selective dopamine D4 receptor blockers, NRA0160 and L-745,870, on A9 and A10 dopamine neurons in rats.
Extracellular single-unit activities of dopamine neurons were recorded using chloral hydrate anaesthetized rats. We examined the reversal effects of the selective dopamine D4 receptor blockers, NRA0160 (2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole) and L-745,870 (3-[[4-(4-chlorophenyl) piperazin-1-yl] methyl]-1H-pyrrolo [2,3-b] pyridine), on dopamine agonists induced inhibition of dopamine neural activity. The firing rates of the substantia nigra pars compacta (A9) and the ventral tegmental area (A10) dopamine neurons were inhibited by methamphetamine (MAP: 1 mg/kg, i.v.) and apomorphine (APO: 40 microg/kg, i.v). NRA0160 dose-dependently reversed the inhibitory effects of MAP and APO on both A9 and A10 dopamine neurons. NRA0160 was more potent in reversing the inhibitory effects of both MAP and APO on A10 than A9 dopamine neurons. L-745,870 failed to reverse the inhibition produced by MAP on A9 and A10 dopamine neurons, whereas L-745,870, at the highest dose used, significantly reversed APO-induced inhibition of A10 but not A9 dopamine neurons. These results suggest that NRA0160 has different electrophysiological profiles on dopaminergic neural activity compared to L-745,870 and may have atypical antipsychotic effects.
Kawashima
N
N
1st Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Saitama, Japan. s16386@ccm.taisho.co.jp
Okuyama
S
S
Omura
T
T
Chaki
S
S
Tomisawa
K
K
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050638:Receptors, Dopamine D4; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493601:Drd4 protein, rat; C121249:NRA 0160; D010880:Piperidines; D011725:Pyridines; D011758:Pyrroles; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D050638:Receptors, Dopamine D4; D004298:Dopamine