Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine
Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine
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DOI：
10.1016/s0924-977x(03)00191-3
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发表时间：
2004-08-01
影响因子：
5.6
通讯作者：
Harro, J
中科院分区：
文献类型：
--
作者：
Alttoa, A;Harro, J
中枢神经系统中多巴胺能神经传递和胆囊收缩素（CCK）之间的相互作用可能在精神障碍和药物滥用的发病机制中起重要作用。在本研究中，我们研究了选择性CCK受体拮抗剂devazepide和L-365,260（分别用于选择性阻断CCK1和CCK2受体）共同给药对安非他明对大鼠探索行为的影响，以及对安非他明运动反应的增敏。安非他明（0.5 mg/kg）连续5天增加了探索箱中的探索活动，而德伐西得（10杯/kg）阻断了安非他明引起的活动刺激，L-365,260（10杯/kg）增强了安非他明引起的活动刺激。德伐昔得与安非他明共给药可抑制对安非他明的致敏，而L-365,260与安非他明共给药可增强安非他明激发剂量的运动效应。这些结果表明，在探索活动中释放的内源性CCK通过作用于两种受体亚型来塑造对安非他明的行为反应，并调节对安非他明的致敏发展。(C) 2003 Elsevier B.V./ECNP。版权所有。
Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in the CNS may be important in the pathogenesis of psychotic disorders and substance abuse. In this study, the effect of coadministration of the selective CCK receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and CCK2 receptors, respectively), on the effect of amphetamine on the rat exploratory behavior, and on sensitization of locomotor response to amphetamine, were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the exploration box for 5 consecutive testing days, while devazepide (10 mug/kg) blocked and L-365,260 (10 mug/kg) enhanced amphetamine-induced stimulation of activity. Devazepide coadministration prevented the development of sensitization to amphetamine, while coadministration of L-365,260 with amphetamine potentiated the locomotor effect of a challenge dose of amphetamine. These results suggest that endogenous CCK, released during exploratory activity, shapes behavioral responses to amphetamine by acting on both receptor subtypes, and modulates the development of sensitization to amphetamine. (C) 2003 Elsevier B.V./ECNP. All rights reserved.