The Effects of mGluR2/3 Activation on Acute and Repeated Amphetamine-Induced Locomotor Activity in Differentially Reared Male Rats
The Effects of mGluR2/3 Activation on Acute and Repeated Amphetamine-Induced Locomotor Activity in Differentially Reared Male Rats
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DOI：
10.1037/a0035273
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发表时间：
2014-06-01
影响因子：
2.3
通讯作者：
Cain, Mary E.
中科院分区：
文献类型：
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作者：
Arndt, David L.;Arnold, Jennifer C.;Cain, Mary E.
环境刺激在影响滥用药物的可能性方面起着关键作用。环境富集可以降低这种可能性。神经递质谷氨酸对药物奖励和饲养引起的大脑变化都有贡献。本研究研究了第2组代谢型谷氨酸受体（mGluR（2/3））激动剂LY-379268（0.5、1.0 mg/kg）对差异饲养雄性大鼠急性和重复安非他明诱导运动活动的影响。雄性Sprague-Dawley大鼠在断奶后被随机分配到3种环境条件之一：富集（EC）、隔离（IC）或标准（SC），在其中饲养30天。评估了LY-379268对急性苯丙胺诱导的自发活动的影响。在注射安非他明（0.5 mg/kg）或生理盐水激发前，对大鼠注射LY-379268（0.5、1.0 mg/kg）或生理盐水。在5个运动阶段之前，还向大鼠注射安非他明（0.5 mg/kg）或盐水。在14-15天的休息期后，在接受安非他明（0.5 mg/kg）前30分钟使用LY-379268（0.5、1.0 mg/kg）或盐水注射评价重复安非他明暴露的影响。结果显示，LY-379268给药呈剂量依赖性衰减急性苯丙胺诱导的运动活动，EC大鼠的衰减通常小于IC或SC大鼠。在重复安非他明给药后，LY-379268减弱差异饲养大鼠中安非他明诱导的运动活性的最终表达的能力具有剂量依赖性。在EC大鼠中观察到的LY-379268的不同作用表明，富集诱导的多巴胺能改变可能防止对精神兴奋剂的敏感性。
Environmental stimuli play a key role in affecting the likelihood to abuse drugs. Environmental enrichment can reduce that likelihood. The neurotransmitter glutamate contributes to both drug reward and rearing-induced changes in the brain. The current study investigated the effects of the Group-2 metabotropic glutamate receptor (mGluR(2/3)) agonist, LY-379268 (0.5, 1.0 mg/kg), on acute and repeated amphetamine-induced locomotor activity in differentially reared male rats. Male Sprague-Dawley rats were randomly assigned to one of 3 environmental conditions postweaning: enriched (EC), isolated (IC), or standard (SC), where they reared for 30 days. The effect of LY-379268 on acute amphetamine-induced locomotor activity was assessed. Rats were injected with either LY-379268 (0.5, 1.0 mg/kg) or saline prior to an amphetamine (0.5 mg/kg) or saline challenge injection. Rats were also administered amphetamine (0.5 mg/kg) or saline injections prior to 5 locomotor sessions. Following a rest period of 14-15 days, the effects of repeated amphetamine exposure were evaluated using LY-379268 (0.5, 1.0 mg/kg) or saline injections 30 min prior to receiving amphetamine (0.5 mg/kg). Results showed that LY-379268 administration dose-dependently attenuated acute amphetamine-induced locomotor activity, with EC rats generally displaying less attenuation than IC or SC rats. After repeated amphetamine administrations, the ability of LY-379268 to attenuate the final expression of amphetamine-induced locomotor activity in differentially reared rats was dose-dependent. The differing effect of LY-379268 observed in EC rats suggests enrichment-induced glutamatergic alterations that may protect against sensitivity to psychostimulants.