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Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors

Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors Abstract The nigrostriatal dopamine system of the mammalian brain is necessary for normal voluntary motor activity. Dopamine exerts its effects by acting on two primary receptor subtypes: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors. Previous research has indicated that both subtypes are involved in the negative feedback regulation of dopamine release in the brain. However, the role of D1-like receptors localized within the striatum remains controversial. Using in vivo microdialysis, we report that infusions of the D1/D5 antagonist SCH 23390 R -(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine (5–200 μM) directly into the striatum increased dopamine release in a concentration-dependent manner. Systemic administration of the novel, full D1/D5 agonist A-77636 (-)-(1 R ,3 S )-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1 H -2-benzopyran produced the opposite effect, a dose-dependent (0.75–3.0 mg/kg s.c.) decrease in striatal dopamine efflux. Infusions of SCH 23390 (5.0 μM) attenuated this decrease. These findings suggest that endogenous dopamine acts on D1-like receptors localized within the striatum to decrease nigrostriatal dopamine release. This negative feedback may be due to the activation of an inhibitory long-loop pathway. Knowledge of the circuitry underlying D1-mediated regulation of nigrostriatal neurons may have significance in current research on treatments for Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Pharmacology and Experimental Therapeutics Am. Soc for Pharma & Experimental Therapeutics

Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors

Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors

The Journal of Pharmacology and Experimental Therapeutics , Volume 311 (1): 342 – Oct 1, 2004

Abstract

Abstract The nigrostriatal dopamine system of the mammalian brain is necessary for normal voluntary motor activity. Dopamine exerts its effects by acting on two primary receptor subtypes: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors. Previous research has indicated that both subtypes are involved in the negative feedback regulation of dopamine release in the brain. However, the role of D1-like receptors localized within the striatum remains controversial. Using in vivo microdialysis, we report that infusions of the D1/D5 antagonist SCH 23390 R -(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine (5–200 μM) directly into the striatum increased dopamine release in a concentration-dependent manner. Systemic administration of the novel, full D1/D5 agonist A-77636 (-)-(1 R ,3 S )-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1 H -2-benzopyran produced the opposite effect, a dose-dependent (0.75–3.0 mg/kg s.c.) decrease in striatal dopamine efflux. Infusions of SCH 23390 (5.0 μM) attenuated this decrease. These findings suggest that endogenous dopamine acts on D1-like receptors localized within the striatum to decrease nigrostriatal dopamine release. This negative feedback may be due to the activation of an inhibitory long-loop pathway. Knowledge of the circuitry underlying D1-mediated regulation of nigrostriatal neurons may have significance in current research on treatments for Parkinson's disease.

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References (45)

Publisher
Am. Soc for Pharma & Experimental Therapeutics
Copyright
Copyright © Journal of Pharmacology and Experimental Therapeutics
ISSN
0022-3565
eISSN
1521-0103
DOI
10.1124/jpet.104.067991
pmid
15175419
Publisher site
See Article on Publisher Site

Abstract

Abstract The nigrostriatal dopamine system of the mammalian brain is necessary for normal voluntary motor activity. Dopamine exerts its effects by acting on two primary receptor subtypes: D1-like (D1 and D5) and D2-like (D2, D3, and D4) receptors. Previous research has indicated that both subtypes are involved in the negative feedback regulation of dopamine release in the brain. However, the role of D1-like receptors localized within the striatum remains controversial. Using in vivo microdialysis, we report that infusions of the D1/D5 antagonist SCH 23390 R -(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H -3-benzazepine (5–200 μM) directly into the striatum increased dopamine release in a concentration-dependent manner. Systemic administration of the novel, full D1/D5 agonist A-77636 (-)-(1 R ,3 S )-3-adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1 H -2-benzopyran produced the opposite effect, a dose-dependent (0.75–3.0 mg/kg s.c.) decrease in striatal dopamine efflux. Infusions of SCH 23390 (5.0 μM) attenuated this decrease. These findings suggest that endogenous dopamine acts on D1-like receptors localized within the striatum to decrease nigrostriatal dopamine release. This negative feedback may be due to the activation of an inhibitory long-loop pathway. Knowledge of the circuitry underlying D1-mediated regulation of nigrostriatal neurons may have significance in current research on treatments for Parkinson's disease.

Journal

The Journal of Pharmacology and Experimental TherapeuticsAm. Soc for Pharma & Experimental Therapeutics

Published: Oct 1, 2004

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