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Reduced basal and ethanol stimulation of striatal extracellular dopamine concentrations in dopamine D2 receptor knockout mice
Author(s) -
Job Martin O.,
Ramachandra Vorani,
Anders Sheneil,
Low Malcolm J.,
Gonzales Rueben A.
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20283
Subject(s) - dopamine , stimulation , dopamine receptor d2 , dopamine receptor , knockout mouse , basal ganglia , chemistry , neuroscience , basal (medicine) , dopamine receptor d1 , extracellular , ethanol , medicine , endocrinology , pharmacology , receptor , biology , central nervous system , biochemistry , insulin
The present study was undertaken to examine the role of the dopamine (DA) D2 receptor in the ethanol‐evoked DA response in the ventral striatum. We performed microdialysis experiments using the D2 null mutant and wild‐type controls and measured the effect of an intraperitoneal (i.p.) injection of either saline or ethanol (2 g/kg) on dialysate DA concentrations in the ventral striatum. Dialysate ethanol concentrations were also determined in the samples from the ventral striatum. In addition, the effects of quinpirole, a D2/D3 agonist, were examined in both the ventral and dorsal striatum. Basal dialysate concentrations of DA were significantly reduced in both the ventral and dorsal striatum of the D2 knockouts compared with wild‐type controls. Ethanol administration significantly enhanced ventral striatal DA in both groups, but the increase in dialysate DA concentration was 3.5‐fold higher in the wild‐type controls. The time course of dialysate ethanol concentrations was similar in the two groups. Saline injection did not alter DA concentrations in either the ventral or dorsal striatum. However, quinpirole (0.3 mg/kg) administration significantly depressed striatal dialysate DA concentrations in the wild‐type mice, but not in the D2 knockouts. The results suggest that the D2 receptor is necessary for normal development and regulation of striatal extracellular DA concentrations, but the mechanism for this alteration is unclear. In addition, the blunted ethanol‐evoked DA response in the D2 knockouts may contribute, in part, to some of the behavioral deficits previously observed in response to ethanol. Synapse 60:158–164, 2006. © 2006 Wiley‐Liss, Inc.