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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism.
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A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism.

机译：一次可卡因暴露通过腹侧被盖区依赖性机制增强了阿片样物质的回报和反感。

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摘要

Repeated exposure to drugs of abuse produces forms of experience-dependent plasticity including behavioral sensitization. Although a single exposure to many addicting substances elicits locomotor sensitization, there is little information regarding the motivational effects of such single exposures. This study demonstrates that a single cocaine exposure enhances both rewarding and aversive forms of opioid place conditioning. Rats were given a single injection of cocaine (15 mg/kg i.p.) in their home cage at different times before conditioning. This treatment enhanced conditioned place preference (CPP) to morphine (2 x 10 mg/kg s.c.) if training began 1 or 5 but not 10 days after the cocaine injection. A single cocaine exposure also enhanced conditioned place aversion (CPA) to the kappa-opioid receptor agonist U69593 (2 x 0.16 mg/kg s.c.). Compared to morphine CPP, U69593 CPA was delayed and persistent. It was not observed at 1 day but appeared if the conditioning began 5 or 10 days after the cocaine injection. Although the cocaine-induced enhancements of both morphine CPP and U69593 CPA followed different time courses, suggesting different mechanisms, both effects were blocked by injection of the N-methyl-d-aspartate receptor antagonist MK-801 (0.5 nmol bilaterally) into the ventral tegmental area, immediately before the cocaine injection. Thus, through a circuit involving the ventral tegmental area, a single cocaine exposure enhanced both micro-opioid receptor reward and kappa-opioid receptor aversion.
机译：反复接触滥用药物会产生依赖于经验的可塑性，包括行为敏感性。尽管一次接触许多成瘾性物质会引起运动性敏化，但是关于这种单一接触的动机影响的信息很少。这项研究表明，一次可卡因暴露可以增强奖励性和厌恶性阿片样物质场所调节作用。在调理之前，在不同的时间给大鼠单次注射可卡因（15 mg / kg腹腔注射）。如果在注射可卡因后的1或5而不是10天开始训练，则该处理可提高对吗啡的条件性位置偏爱（CPP）对吗啡（2 x 10 mg / kg s.c.）。一次可卡因暴露也增强了对κ阿片受体激动剂U69593的条件位置厌恶（CPA）（2 x 0.16 mg / kg s.c.）。与吗啡CPP相比，U69593 CPA延迟且持久。在第1天没有观察到这种情况，但在注射可卡因后5或10天开始调理时出现。尽管可卡因诱导的吗啡CPP和U69593 CPA的增强遵循不同的时间进程，表明机制不同，但这两种作用均通过将N-甲基-d-天冬氨酸受体拮抗剂MK-801（双侧0.5 nmol）注入腹侧而被阻断。在可卡因注射之前的被盖区域。因此，通过涉及腹侧被盖区的回路，单次可卡因暴露既增强了微阿片受体的奖励，又提高了κ-阿片受体的厌恶感。

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