Reduced basal and ethanol stimulation of striatal extracellular dopamine concentrations in dopamine D2 receptor knockout mice

被引:9
作者
Job, Martin O.
Ramachandra, Vorani
Anders, Shhneil
Low, Malcolm J.
Gonzales, Rueben A.
机构
[1] Univ Texas, Austin, TX 78712 USA
[2] Oregon Hlth & Sci Univ, Ctr Study Weight Regulat, Portland, OR USA
[3] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR USA
[4] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR USA
关键词
microdialysis; ventral striatum; dorsal striatum; pharmacokinetics; autoreceptor;
D O I
10.1002/syn.20283
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 wildtype 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.
引用
收藏
页码:158 / 164
页数:7
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