Laboratorio de Farmacología y Conducta, Instituto de Neurociencias, CUCBA, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Laboratorio de Farmacología y Conducta, Instituto de Neurociencias, CUCBA, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Pharmacol Biochem Behav. 2020 Jul;194:172936. doi: 10.1016/j.pbb.2020.172936. Epub 2020 May 1.
Rats exposed prenatally to alcohol show a reduction in the spontaneous activity of dopaminergic neurons of the ventral tegmental area (VTA), as well as greater impulsive behavior and motor activity, behavioral alterations that have been related to dopaminergic dysfunction. Modafinil (MOD) is a dopamine (DA) reuptake blocker prescribed to treat sleep disorders; however, in recent years it has been used for the treatment of ADHD with positive results. Also, studies in humans and rodents show beneficial effects on learning and attention; however, studies evaluating MOD effects on impulsivity are few and show contradictory results. The purpose of this work was to evaluate the effect of a daily dose of MOD (60 mg/kg i.g.) on cognitive (or choice) impulsivity and motor activity in male preadolescent rats exposed prenatally to alcohol or sucrose (isocaloric control). MOD reduced the impulsive responses in a delay discounting task (DDT) at the same time that increased the motor activity, in both healthy and prenatal alcohol treated rats; however, MOD reduced the response latency in DDT only in prenatal alcohol treated rats. This differential effect of DA activation on impulsivity and motor activity show that the MOD dose that improves the impulse control, does not necessarily decrease motor activity, and suggests a possible differential neural mechanism underlying the expression of these behaviors. On the other hand, the changes in the response latency, only in prenatal alcohol treated groups, suggest that decision-making in animals with a dopaminergic dysfunction is more susceptible to be affected by MOD action.
孕期暴露于酒精的大鼠表现出腹侧被盖区(VTA)多巴胺能神经元自发性活动减少,以及更高的冲动行为和运动活性,这些行为改变与多巴胺能功能障碍有关。莫达非尼(MOD)是一种多巴胺(DA)再摄取抑制剂,用于治疗睡眠障碍;然而,近年来,它已被用于治疗 ADHD,并取得了积极的效果。此外,在人类和啮齿动物中的研究表明,它对学习和注意力有有益的影响;然而,评估 MOD 对冲动性影响的研究很少,且结果相互矛盾。本工作的目的是评估每日剂量的 MOD(60mg/kg 腹腔注射)对雄性未成年酒精暴露或蔗糖(等热量对照)预处理大鼠认知(或选择)冲动性和运动活性的影响。MOD 降低了在延迟折扣任务(DDT)中冲动反应的次数,同时增加了健康和酒精预处理大鼠的运动活性;然而,MOD 仅降低了酒精预处理大鼠在 DDT 中的反应潜伏期。这种 DA 激活对冲动性和运动活性的不同影响表明,改善冲动控制的 MOD 剂量不一定会降低运动活性,并提示这些行为表达的潜在不同神经机制。另一方面,只有在酒精预处理组中,反应潜伏期的变化表明,在多巴胺能功能障碍的动物中,决策更容易受到 MOD 作用的影响。