Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats
Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats
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DOI：
10.1523/jneurosci.0529-04.2004
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发表时间：
2004-05-05
影响因子：
5.3
通讯作者：
Wightman, RM
中科院分区：
文献类型：
--
作者：
Cheer, JF;Wassum, KM;Wightman, RM
多巴胺能神经传递与许多滥用物质（包括大麻）的强化特性密切相关。大麻素激活腹侧被盖区多巴胺能神经元，中皮质边缘多巴胺系统的主要上行投射，并通过增加爆发中的冲动数量和提高爆发频率来改变其尖峰模式。虽然他们也增加了时间平均纹状体多巴胺水平的延长时间，很少有人知道这种变化的时间结构。为了阐明这一点，快速扫描循环伏安法被用来监测细胞外多巴胺在自由活动的大鼠延髓核亚秒级的时间尺度分辨率。静脉内施用中枢大麻素（CB 1）受体激动剂R（+）-[2，3-二氢-5-甲基-3-[（吗啉基）甲基]吡咯并[1，2，3-de]-1，4-苯并恶嗪-6-基]-（1-萘基）甲酮甲磺酸盐，剂量依赖性产生的僵住症，运动减少，并降低电诱发多巴胺释放的幅度，同时显著增加检测到的频率。（非刺激）多巴胺浓度瞬变。CB 1受体拮抗剂[N-哌啶基-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基吡唑-3-甲酰胺]逆转并阻止了所有激动剂诱导的效应，但单独注射时对多巴胺释放无影响。这些数据表明，已知增加爆发放电的大麻素激动剂的剂量在延髓核中以先前未识别的时间尺度产生细胞外多巴胺的持续波动。
Dopaminergic neurotransmission has been highly implicated in the reinforcing properties of many substances of abuse, including marijuana. Cannabinoids activate ventral tegmental area dopaminergic neurons, the main ascending projections of the mesocorticolimbic dopamine system, and change their spiking pattern by increasing the number of impulses in a burst and elevating the frequency of bursts. Although they also increase time-averaged striatal dopamine levels for extended periods of time, little is known about the temporal structure of this change. To elucidate this, fast-scan cyclic voltammetry was used to monitor extracellular dopamine in the nucleus accumbens of freely moving rats with subsecond timescale resolution. Intravenous administration of the central cannabinoid (CB1) receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl) methanone mesylate, dose-dependently produced catalepsy, decreased locomotion, and reduced the amplitude of electrically evoked dopamine release while markedly increasing the frequency of detected (nonstimulated) dopamine concentration transients. The CB1 receptor antagonist [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide] reversed and prevented all agonist-induced effects but did not show effects on dopamine release when injected alone. These data demonstrate that doses of a cannabinoid agonist known to increase burst firing produce ongoing fluctuations in extracellular dopamine on a previously unrecognized temporal scale in the nucleus accumbens.