Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants
Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants
复制标题
DOI：
10.1124/jpet.105.091678
复制
发表时间：
2005-12-01
影响因子：
3.5
通讯作者：
Bannon, AW
中科院分区：
文献类型：
--
作者：
Couceyro, PR;Evans, C;Bannon, AW
毒瘾源于对控制动机的神经回路的颠覆。虽然精神刺激剂和滥用药物的享乐性和成瘾性主要归因于多巴胺和谷氨酸，但人们意识到大脑中的其他信号分子也很重要。这项研究表明，可卡因和安非他明调节转录物(CART)多肽调节精神刺激剂的运动和动机特性。在CART(Tm1Amgen)、Cart KO(CART KO)和野生型(WT)小鼠中观察了可卡因和苯丙胺对行为的影响。急性给予苯丙胺增加了WT小鼠的运动活动，但这种反应在CART KO小鼠中减弱。反复使用安非他明可使WT小鼠产生运动敏化，但在Cart KO小鼠中几乎没有。安非他明在两种基因型鼠中都引起条件性位置偏爱，但在Cart KO小鼠中，安非他明的效力降低。在两种基因型中都观察到静脉注射可卡因，但Cart KO小鼠比WT小鼠消耗更少的可卡因，对可卡因的反应也更少。在突变的Cart KO小鼠中，精神刺激剂的行为效应降低。相比之下，未服药的WT小鼠和CART KO小鼠的旷场活动和对蔗糖的偏好没有显著差异。苯丙胺和可卡因对CART KO小鼠的减弱作用表明CART肽在运动中具有积极的神经调节作用，并提示CART肽在精神刺激剂成瘾中具有积极的神经调节作用和精神刺激剂的激励特性。
Drug addiction results from a subversion of neural circuits that control motivation. Although the hedonic and addictive properties of psychostimulants and drugs of abuse are predominantly attributed to dopamine and glutamate, it is appreciated that other signaling molecules in the brain are important. This study suggests that cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants. The behavioral effects of cocaine and amphetamine were examined in Cart(tm1Amgen) knockout (Cart KO) and wild- type (WT) mice. Acute amphetamine administration increased in locomotor activity in WT mice, but this response was attenuated in Cart KO mice. Repeated amphetamine produced locomotor sensitization in WT mice but hardly any in Cart KO mice. Amphetamine elicited conditioned place preference in both genotypes, but amphetamine's potency was reduced in the Cart KO mice. Intravenous cocaine self-administration was observed in both genotypes, but Cart KO mice consumed less cocaine and responded less for cocaine than WT mice. The behavioral effects of psychostimulants were reduced in the mutant Cart KO mice. By contrast, open field activity and sucrose preference of drug-naive mice WT and Cart KO mice were not significantly different. The attenuated effects of amphetamine and cocaine in Cart KO mice suggest a positive neuromodulatory role for CART peptides in the locomotor and motivational properties of psychostimulants and implicate CART peptides in psychostimulant addiction.