Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum:: an in vivo microdialysis study in rats
Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum:: an in vivo microdialysis study in rats
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DOI：
10.1111/j.1460-9568.2004.03497.x
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Parsons, LH
中科院分区：
文献类型：
--
作者：
Caillé, S;Parsons, LH
一些证据表明，阿片诱导的腹侧苍白球去抑制参与阿片奖励的调解，虽然直接在体内的证据来支持这一假设一直缺乏。本实验测试这一假设，通过调查腹侧苍白球氨基酸流出的变化，在体内微透析过程中正在进行的静脉注射海洛因自我管理的大鼠。腹侧苍白球透析液中抑制性氨基酸GABA的浓度在海洛因自我给药的前10分钟内显著降低（每次输注0.02 mg; FR-1），并在3小时自我给药期的剩余时间内保持约65%的预基线水平。透析液谷氨酸水平在海洛因摄入的第一个小时内没有变化，但在随后的2小时自我给药期间显著增加至约120%的稳定水平。因此，海洛因自我管理与减少GABA流出和后期增加谷氨酸流出腹侧苍白球。这些观察结果与海洛因自我给药导致腹侧苍白球去抑制和/或兴奋的假设一致。
Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained approximate to65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of approximate to120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum.