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Behavioural and dopaminergic alterations induced by a low dose of WIN 55,212-2 in a conditioned place preference procedure.

机译:低剂量的WIN 55,212-2在条件性场所偏爱程序中诱发的行为和多巴胺能改变。

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AIMS: This study investigated the role of the cannabinoid CB1 receptor agonist, WIN 55,212-2, on motor activity. Subsequently, the effects of a low, stimulatory dose of WIN 55,212-2 and cocaine, as a positive control, were evaluated using a conditioned place preference (CPP) procedure. Upon completion of CPP, in rats that had been treated with WIN 55,212-2, dopaminergic status and spontaneous and d-amphetamine-induced motor activity were assessed. MAIN METHODS: Sprague-Dawley rats were evaluated for habituated motor activity following WIN 55,212-2 (0, 0.1, 0.3, 1 mg/kg, i.p.) administration. A stimulatory dose of WIN 55,212-2 (0.1 mg/kg, i.p.) and cocaine (20 mg/kg, i.p.) was selected to assess CPP behaviour. Upon completion of CPP, in one group, tissue levels of dopamine and its metabolites were measured in distinct brain regions (dorsal striatum, nucleus accumbens, prefrontal cortex, amygdala, hippocampus) using High Performance Liquid Chromatography with electrochemical detection. In another group, spontaneous and D-amphetamine-induced motor activity was evaluated in an open-field apparatus. KEY FINDINGS: The lowest dose of WIN 55,212-2 increased motor activity but did not produce CPP. As expected, cocaine induced clear CPP. Dopaminergic status was increased in a region-specific way and motor activity was enhanced following a challenge of D-amphetamine in rats that had been administered with WIN 55,212-2 during conditioning. SIGNIFICANCE: A stimulatory effect of WIN 55,212-2 on motor activity was not accompanied by place preference. Upon completion of the CPP procedure, this dose was found to induce region-specific hyperdopaminergia along with a greater sensitivity to a subsequent challenge dose of D-amphetamine.
机译:目的:这项研究调查了大麻素CB1受体激动剂WIN 55,212-2在运动活动中的作用。随后,使用条件性位置偏爱(CPP)程序评估了低刺激剂量的WIN 55,212-2和可卡因作为阳性对照的效果。 CPP完成后,在用WIN 55,212-2治疗的大鼠中,评估多巴胺能状态以及自发和d-苯异丙胺诱导的运动活动。主要方法:在给予WIN 55,212-2(0,0.1,0.3,1 mg / kg,i.p.)后,评估Sprague-Dawley大鼠的习惯性运动活动。选择WIN 55,212-2(0.1 mg / kg,i.p.)和可卡因(20 mg / kg,i.p.)的刺激剂量来评估CPP行为。 CPP完成后,一组患者使用高效液相色谱和电化学检测技术在不同的大脑区域(背侧纹状体,伏隔核,前额叶皮层,杏仁核,海马体)中测量多巴胺及其代谢物的组织水平。在另一组中,在开放视野的装置中评估了自发的和D-苯异丙胺诱导的运动活动。主要发现:最低剂量的WIN 55,212-2可增加运动活性,但不产生CPP。如预期的那样,可卡因引起了清晰的CPP。多巴胺能状态以区域特定的方式增加,并且在调节过程中以WIN 55,212-2给药的大鼠受到D-苯异丙胺的攻击后,运动能力得到增强。重要性:WIN 55,212-2对运动活动的刺激作用并未伴随位置偏好。 CPP程序完成后,发现该剂量可诱发区域特异性多巴胺痛,并且对随后的D-苯异丙胺激发剂量具有更高的敏感性。

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