Evidence for a functional role of dopamine type-1 (D-1) receptors in the substantia nigra of rats

Roberts T. Matthews; Dwight C. German

doi:10.1016/0014-2999(86)90644-8

Evidence for a functional role of dopamine type-1 (D-1) receptors in the substantia nigra of rats

Roberts T. Matthews, Dwight C. German

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Abstract

The microiontophoretic application of dopamine onto neurons in the substantia nigra of rats increased the spontaneous activity of zona reticulata (ZR) neurons but decreased the activity of zone compacta (ZC) neurons. The systemic administration of the dopamine antagonists, haloperidol and cis-flupentixol, blocked the dopamine effects. However, haloperidol was more potent on ZC neurons that on ZR neurons whereas cis-flupentixol was of comparable potency on ZC and ZR neurons. In addition, microiontopheretic application of a cyclic adenosine monophosphate analog was found to mimic the effects of dopamine on ZR neurons, but not on ZC neurons. Taken together with receptor binding studies on the relative affinities of haloperidol and cis-flupentixol for various dopamine receptor subtypes, these data suggest that the excitatory effect of dopamine on ZR neurons is mediated by a D-1 type receptor whereas its inhibitory effect on the ZC dopaminergic neuron is mediated by a D-2 type receptor.

Original language	English (US)
Pages (from-to)	87-93
Number of pages	7
Journal	European Journal of Pharmacology
Volume	120
Issue number	1
DOIs	https://doi.org/10.1016/0014-2999(86)90644-8
State	Published - Jan 14 1986

Keywords

D-1 receptors
Dopamine
Neuroleptics
Substantia nigra
cAMP

ASJC Scopus subject areas

Pharmacology

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10.1016/0014-2999(86)90644-8

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title = "Evidence for a functional role of dopamine type-1 (D-1) receptors in the substantia nigra of rats",

abstract = "The microiontophoretic application of dopamine onto neurons in the substantia nigra of rats increased the spontaneous activity of zona reticulata (ZR) neurons but decreased the activity of zone compacta (ZC) neurons. The systemic administration of the dopamine antagonists, haloperidol and cis-flupentixol, blocked the dopamine effects. However, haloperidol was more potent on ZC neurons that on ZR neurons whereas cis-flupentixol was of comparable potency on ZC and ZR neurons. In addition, microiontopheretic application of a cyclic adenosine monophosphate analog was found to mimic the effects of dopamine on ZR neurons, but not on ZC neurons. Taken together with receptor binding studies on the relative affinities of haloperidol and cis-flupentixol for various dopamine receptor subtypes, these data suggest that the excitatory effect of dopamine on ZR neurons is mediated by a D-1 type receptor whereas its inhibitory effect on the ZC dopaminergic neuron is mediated by a D-2 type receptor.",

keywords = "D-1 receptors, Dopamine, Neuroleptics, Substantia nigra, cAMP",

author = "Matthews, {Roberts T.} and German, {Dwight C.}",

note = "Funding Information: This research was supported by a Biomedical Research Support Grant from Texas A&M University and MH-40774 (RTM), and grant MH-30546 (DCG). The authors wish to thank H. Lundbeck & Co. A/S for the gift of cis-flupentixol and McNeil Pharmaceutical for the gift of haloperidol. The authors also wish to thank Mildred Kreitzer, Janet Natowitz and Laura Boynton for secretarial assistance and Evelyn Kapes, Kathy McDermott and Sasan Askari for technical assistance.",

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AU - German, Dwight C.

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PY - 1986/1/14

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N2 - The microiontophoretic application of dopamine onto neurons in the substantia nigra of rats increased the spontaneous activity of zona reticulata (ZR) neurons but decreased the activity of zone compacta (ZC) neurons. The systemic administration of the dopamine antagonists, haloperidol and cis-flupentixol, blocked the dopamine effects. However, haloperidol was more potent on ZC neurons that on ZR neurons whereas cis-flupentixol was of comparable potency on ZC and ZR neurons. In addition, microiontopheretic application of a cyclic adenosine monophosphate analog was found to mimic the effects of dopamine on ZR neurons, but not on ZC neurons. Taken together with receptor binding studies on the relative affinities of haloperidol and cis-flupentixol for various dopamine receptor subtypes, these data suggest that the excitatory effect of dopamine on ZR neurons is mediated by a D-1 type receptor whereas its inhibitory effect on the ZC dopaminergic neuron is mediated by a D-2 type receptor.

AB - The microiontophoretic application of dopamine onto neurons in the substantia nigra of rats increased the spontaneous activity of zona reticulata (ZR) neurons but decreased the activity of zone compacta (ZC) neurons. The systemic administration of the dopamine antagonists, haloperidol and cis-flupentixol, blocked the dopamine effects. However, haloperidol was more potent on ZC neurons that on ZR neurons whereas cis-flupentixol was of comparable potency on ZC and ZR neurons. In addition, microiontopheretic application of a cyclic adenosine monophosphate analog was found to mimic the effects of dopamine on ZR neurons, but not on ZC neurons. Taken together with receptor binding studies on the relative affinities of haloperidol and cis-flupentixol for various dopamine receptor subtypes, these data suggest that the excitatory effect of dopamine on ZR neurons is mediated by a D-1 type receptor whereas its inhibitory effect on the ZC dopaminergic neuron is mediated by a D-2 type receptor.

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Evidence for a functional role of dopamine type-1 (D-1) receptors in the substantia nigra of rats

Abstract

Keywords

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