Millenium Science Nucleus in Stress and Addiction, Pontificia Universidad Católica de Chile, Santiago, Chile.
Neurochem Int. 2012 Mar;60(4):344-9. doi: 10.1016/j.neuint.2012.01.014. Epub 2012 Jan 28.
The effects after the acute activation of the kappa opioid receptor (KOR) can be distinguished from the effect after repeated administration of KOR agonist. Here, we report the effect of repeated administration of U69593 during abstinence after amphetamine-induced locomotor sensitization. Rats were injected once daily with amphetamine for five consecutive days. From day 6 to 9, rats that developed locomotor sensitization, received once daily injection of U69593 or vehicle. On day 10, all rats were injected with a challenging dose of amphetamine and locomotor activity was measured to assess the expression of sensitization. Microdialysis studies were carried out to assess dopamine extracellular levels in NAc. Rats that develop and express horizontal locomotor sensitization to amphetamine show increased dopamine release in the NAc induced by high K(+). The repeated treatment with U69593 reverses the sensitized depolarization-stimulated dopamine release in the NAc, but not the expression of locomotor sensitization induced by amphetamine. Thus, repeated activation of KORs during early amphetamine withdrawal dissociates the behavioral responses and the neurochemical responses that accompany the expression of sensitization to amphetamine.
κ 阿片受体（KOR）的急性激活后的影响与 KOR 激动剂重复给药后的影响不同。在这里，我们报告了在安非他命诱导的运动敏化戒断期间重复给予 U69593 的效果。大鼠每天接受安非他命注射一次，连续五天。从第 6 天到第 9 天，对出现运动敏化的大鼠，每天给予 U69593 或载体注射。第 10 天，所有大鼠均接受安非他命的挑战剂量注射，并测量运动活动以评估敏化的表达。微透析研究用于评估 NAc 中的多巴胺细胞外水平。对安非他命产生和表达水平运动敏化的大鼠，在 NAc 中显示出由高 K+诱导的多巴胺释放增加。U69593 的重复治疗逆转了 NAc 中敏化的去极化刺激的多巴胺释放，但不能逆转安非他命诱导的运动敏化的表达。因此，在安非他命早期戒断期间，重复激活 KORs 可分离伴随安非他命敏化表达的行为反应和神经化学反应。
