DOPAMINERGIC ANTAGONISM WITHIN THE NUCLEUS-ACCUMBENS OR THE AMYGDALA PRODUCES DIFFERENTIAL-EFFECTS ON INTRAVENOUS COCAINE SELF-ADMINISTRATION UNDER FIXED AND PROGRESSIVE RATIO SCHEDULES OF REINFORCEMENT
DOPAMINERGIC ANTAGONISM WITHIN THE NUCLEUS-ACCUMBENS OR THE AMYGDALA PRODUCES DIFFERENTIAL-EFFECTS ON INTRAVENOUS COCAINE SELF-ADMINISTRATION UNDER FIXED AND PROGRESSIVE RATIO SCHEDULES OF REINFORCEMENT
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DOI：
10.1016/0006-8993(93)90084-z
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发表时间：
1993-10-08
期刊：
影响因子：
2.9
通讯作者：
ROBERTS, DCS
中科院分区：
文献类型：
--
作者：
MCGREGOR, A;ROBERTS, DCS
在静脉注射可卡因自我给药前即刻，向丘脑核（NACC）或杏仁核（AMY）中给予双侧脑内注射D1受体拮抗剂SCH 23390。在固定比例（FR）强化时间表（1.5 mg/kg/注射）下，向两个部位注射产生剂量依赖性（0.1-2.0 μ g/注射）可卡因自我给药率增加。然而，注射到AMY产生了显着更大的药物摄入率比NACC内的增加。相比之下，在可卡因强化的累进比率（PR）计划下，D1拮抗剂在AMY内对断点（BP）的影响很小，但在注射到NACC后大大降低了BP。自发活动研究显示，在全身注射可卡因（10 mg/kg i. p.）后，SCH 23390（1.0 μ g/注射部位）在注射至任一脑部位后，可显著降低活性至相当水平。这表明可卡因自我给药范例中两个神经位点之间的效应分离似乎不是由于NACC内拮抗剂的运动减少作用更大。这些结果表明，一个显着的贡献是由AMY多巴胺可卡因的强化机制，这似乎是不同的NACC。此外，他们认为FR和PR时间表可以测量可卡因的CNS作用的不同方面，这些作用支持自我给药行为。
Bilateral intracerebral injections of the D1 receptor antagonist, SCH 23390, were administered into the nucleus accumbens (NACC) or amygdala (AMY) immediately prior to an i.v. cocaine self-administration session. Injection into both sites produced a dose-dependent (0.1-2.0 mug/injection) increase in the rate of cocaine self-administration under a fixed ratio (FR) schedule of reinforcement (1.5 mg/kg/injection). However, injection into the AMY produced a significantly greater increase in rate of drug intake than within the NACC. In contrast, under a progressive ratio (PR) schedule of cocaine reinforcement the D1 antagonist had very little effect within the AMY on break point (BP) but greatly reduced the BP following injection into the NACC. A locomotor activity study revealed that following systemic injection of cocaine (10 mg/kg i.p.), SCH 23390 (1.0 mug/injection site) significantly reduced activity to comparable levels following injection into either brain site. This indicates that the dissociation of effects between the two neural sites within the cocaine self-administration paradigm does not appear to be due to greater locomotor reducing actions of the antagonist within the NACC. These results demonstrate that a significant contribution is made by AMY dopamine to cocaine reinforcement mechanisms, which appears to be different to that of the NACC. Moreover, they suggest that FR and PR schedules may measure different aspects of cocaine's CNS action which support self-administration behaviour.