DELTA-9-TETRAHYDROCANNABINOL PRODUCES NALOXONE-BLOCKABLE ENHANCEMENT OF PRESYNAPTIC BASAL DOPAMINE EFFLUX IN NUCLEUS-ACCUMBENS OF CONSCIOUS, FREELY-MOVING RATS AS MEASURED BY INTRACEREBRAL MICRODIALYSIS
DELTA-9-TETRAHYDROCANNABINOL PRODUCES NALOXONE-BLOCKABLE ENHANCEMENT OF PRESYNAPTIC BASAL DOPAMINE EFFLUX IN NUCLEUS-ACCUMBENS OF CONSCIOUS, FREELY-MOVING RATS AS MEASURED BY INTRACEREBRAL MICRODIALYSIS
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DOI：
10.1007/bf02245916
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发表时间：
1990-01-01
影响因子：
3.4
通讯作者：
GARDNER, EL
中科院分区：
文献类型：
--
作者：
CHEN, JP;PAREDES, W;GARDNER, EL
本研究检查了大麻中的精神活性成分Δ-9-四氢大麻酚（Δ 9-THC）的急性给药对多巴胺（DA）及其代谢物的细胞外流出的影响，如通过在清醒的自由移动大鼠的延髓核中的体内微透析所测量的。显著增强脑刺激奖赏（颅内自我刺激）的低剂量（0.5-1.0 mg/kg）的Δ 9-THC显著增加丘脑核中的DA流出。通过从灌注液中除去钙（Ca++）离子，消除了Δ 9-THC对DA流出的增强，表明Δ 9-THC的作用具有Ca++依赖性。通过剂量低至0.1mg/kg的纳洛酮，Δ 9-THC对DA流出的增强被完全阻断或显著减弱。假设中皮质边缘DA回路在介导和/或调节脑刺激奖励中的作用，目前的数据提出了大麻的奖励作用的可能性，因此其兴奋作用和滥用潜力可能与突触前DA机制的药理学增强有关。此外，大麻增强的DA机制似乎受到内源性阿片肽系统的调节。
This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (.DELTA.9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopaine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. .DELTA.9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by .DELTA.9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca++-dependence of .DELTA.9-THC''s action. Augmentation of DA efflux by .DELTA.9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana''s rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.