Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Neuroscience. 2011 Aug 25;189:178-86. doi: 10.1016/j.neuroscience.2011.05.028. Epub 2011 May 27.
Behavioral sensitization to the stimulating effect of ethanol (EtOH) or other drugs, which can be observed in mice as an increase in locomotor activity after repeated administration, has been associated with neuroadaptations within the dopaminergic mesolimbic pathway. In the nucleus accumbens (NAc), an afferent region of the mesolimbic pathway, dopamine (DA) release can be modulated by serotonergic 2C receptors (5-HT2CR). The aim of the present study was to evaluate the function of 5-HT2CR in the expression of EtOH-induced behavioral sensitization in Albino Swiss mice with various levels of sensitization to EtOH. In the four experiments that we performed, the mice were given saline or 2.2 g/kg EtOH daily for 21 days. Based on their locomotion on day 21, the EtOH-pretreated mice were assigned to one of two groups, highly sensitized or weakly sensitized to the stimulating effect of EtOH. In each experiment, 2 weeks after the 21-day treatment (withdrawal period), the mice were submitted to four pharmacological challenges of two drug treatments each. The mice in experiments 1 and 2 received two i.p. injections, whereas the mice in experiments 3 and 4 received an intra-NAc administration followed by an i.p. injection. The challenges were: saline+saline; saline+EtOH; SB-242084 (a 5-HT2CR antagonist; 0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 μg/side intra-NAc)+EtOH; and SB-242084 (0.5, 1.0 or 2.0 mg/kg i.p. or 1.0 or 2.0 μg/side intra-NAc)+saline. At all tested doses, i.p. administration of SB-242084 did not affect the stimulating effect of EtOH in the highly sensitized mice. However, when delivered by intra-NAc administration, SB-242084 reduced (at 1.0 μg/side) or completely blocked (at 2.0 μg/side) the expression of EtOH-induced behavioral sensitization in the highly sensitized mice. These findings suggest that the expression of behavioral sensitization to the stimulating effect of EtOH depends on accumbal 5-HT2CR activity.
行为对乙醇（EtOH）或其他药物的刺激作用的敏感化，在老鼠中可以表现为反复给药后运动活动的增加，这与多巴胺能中脑边缘途径内的神经适应有关。在伏隔核（NAc）中，中脑边缘途径的一个传入区域，多巴胺（DA）释放可以被 5-羟色胺 2C 受体（5-HT2CR）调节。本研究的目的是评估 5-HT2CR 在不同程度对 EtOH 敏感的白化瑞士小鼠中 EtOH 诱导的行为敏感化表达中的功能。在我们进行的四项实验中，小鼠每天给予生理盐水或 2.2 g/kg EtOH，共 21 天。根据它们在第 21 天的运动情况，将 EtOH 预处理的小鼠分为两组，一组对 EtOH 的刺激作用高度敏感，另一组对 EtOH 的刺激作用低度敏感。在每个实验中，在 21 天治疗（停药期）后 2 周，将小鼠进行两次药物治疗各两次的四次药理学挑战。实验 1 和 2 的小鼠接受两次腹腔注射，而实验 3 和 4 的小鼠接受一次 NAc 内给药，然后进行腹腔注射。挑战如下：生理盐水+生理盐水；生理盐水+EtOH；SB-242084（5-HT2CR 拮抗剂；0.5、1.0 或 2.0 mg/kg 腹腔内或 1.0 或 2.0 μg/侧 NAc 内）+EtOH；和 SB-242084（0.5、1.0 或 2.0 mg/kg 腹腔内或 1.0 或 2.0 μg/侧 NAc 内）+生理盐水。在所有测试剂量下，腹腔内给予 SB-242084 均不影响高度敏感小鼠中 EtOH 的刺激作用。然而，当通过 NAc 内给药时，SB-242084 减少（1.0 μg/侧）或完全阻断（2.0 μg/侧）高度敏感小鼠中 EtOH 诱导的行为敏感化的表达。这些发现表明，对 EtOH 刺激作用的行为敏感化的表达取决于伏隔核内 5-HT2CR 活性。
