D1 receptor stimulation inhibits dopamine cell activity after reserpine treatment but not after chronic SCH 23390: an effect blocked by N-methyl-D-aspartate antagonists.
Single unit recordings were conducted to examine the effects of systemic D1 agonist SKF 38393 on the firing rate of substantia nigra pars compacta dopamine (DA) neurons in rats pretreated subchronically with reserpine or chronically with a D1 antagonist. The effect of N-methyl-D-aspartate receptor antagonists on these processes was also investigated. An i.v. injection of SKF 38393 (10 mg/kg) significantly inhibited DA cell activity by approximately 70% in rats pretreated with reserpine (1 mg/kg, s.c.) for 6 days and studied under conditions of local anesthesia. SKF 38393 exerted no effect in reserpinized rats anesthetized with chloral hydrate. The SKF 38393-induced inhibition was reversed by the D1 antagonist SCH 23390, but not by the preferential D2 antagonist haloperidol. This effect of SKF 38393 was observed in 60% of the rats as early as 3 to 8 hr after the first reserpine injection, and the inhibition remained significant 5 to 15 days (averaging 64 and 58%) after termination of the 6-day reserpine treatment. The N-methyl-D-aspartate antagonists ketamine, at anesthetic doses (100 mg/kg, i.p.), and MK 801, at a nonanesthetic dose (0.15 mg/kg, i.v.), completely blocked the inhibitory effect of SKF 38393. In contrast, DA cells recorded in rats pretreated with SCH 23390 for 7 to 21 days, followed by a 4-day washout period, failed to respond to SKF 38393. Because nigrostriatal DA neurons do not appear to express D1 receptors, these results suggest that D1 receptors can exert an indirect inhibitory effect on the activity of nigral DA neurons, presumably through striatonigral neuronal pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
Huang
K X
KX
Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Walters
J R
JR
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002697:Chloral Hydrate / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012110:Reserpine / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D002697:Chloral Hydrate; D007649:Ketamine; D016291:Dizocilpine Maleate; D012110:Reserpine; D004298:Dopamine