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PMID:16490190

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Citation

Roberts, C, Cummins, R, Gnoffo, Z and Kew, JN (2006) Dopamine D3 receptor modulation of dopamine efflux in the rat nucleus accumbens. Eur. J. Pharmacol. 534:108-14

Abstract

The effect of antipsychotics on electrically evoked dopamine efflux in the rat nucleus accumbens core and shell was investigated, using in vitro fast cyclic voltammetry. In the nucleus accumbens core, the dopamine D2/D3 receptor agonist, (+/-)7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene), inhibited dopamine efflux with a pEC50 of 8.1. Clozapine, haloperidol, sulpiride and the selective dopamine D3 receptor antagonist, SB-277011-A, had no effect on dopamine efflux per se but all attenuated the (+/-)7-OH-DPAT-induced-inhibition of dopamine efflux, with pA2 values of 6.6, 7.9, 7.0 and 7.6, respectively. In the nucleus accumbens shell, (+/-)7-OH-DPAT inhibited dopamine efflux with a pEC50 of 8.3. Clozapine and SB-277011-A had no effect on dopamine efflux. In contrast, haloperidol and sulpiride significantly increased dopamine efflux through a D2 receptor-mediated mechanism. Clozapine, haloperidol, sulpiride and SB-277011-A attenuated the (+/-)7-OH-DPAT-induced inhibition with pA2 values of 7.3, 8.6, 7.6 and 8.2, respectively. These data demonstrate that dopamine efflux is modulated by both dopamine D2 and D3 receptors in the rat nucleus accumbens.

Links

PubMed Online version:10.1016/j.ejphar.2006.01.014

Keywords

Animals; Antipsychotic Agents/pharmacology; Clozapine/pharmacology; Dopamine/metabolism; Dopamine Agonists/pharmacology; Dopamine Antagonists/pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Haloperidol/pharmacology; Male; Nitriles/pharmacology; Nucleus Accumbens/drug effects; Nucleus Accumbens/metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2/drug effects; Receptors, Dopamine D3/drug effects; Sulpiride/pharmacology; Tetrahydroisoquinolines/pharmacology; Tetrahydronaphthalenes/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DRD3

involved_in

GO:0014059: regulation of dopamine secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD2

involved_in

GO:0033602: negative regulation of dopamine secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD3

involved_in

GO:0007212: dopamine receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD3

enables

GO:0008144: drug binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:DRD3

enables

GO:0035240: dopamine binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:DRD3

enables

GO:0004952: dopamine neurotransmitter receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

RAT:DRD3

involved_in

GO:0001963: synaptic transmission, dopaminergic

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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