Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Argentina.
Pharmacol Biochem Behav. 2019 Jun;181:60-68. doi: 10.1016/j.pbb.2019.04.005. Epub 2019 Apr 18.
Adolescents are more sensitive than adults to the neural and behavioral effects of psychostimulants, and exhibit greater vulnerability to drug abuse, dependence or relapse into these conditions. We have reported that cocaine pretreatment during adolescence promotes the expression of behavioral sensitization to a greater extent than when the pretreatment occurs at adulthood. Behavioral sensitization has been associated to the transition from drug use to addiction and is postulated to indicate heightened sensitivity to the appetitive motivational effects of drugs. The relationship between behavioral sensitization and conventional measures of drug reward, such as conditioned place preference (CPP), has yet to be thoroughly investigated, and little is known about age-related differences in this phenomenon. The present study tested cocaine-induced CPP in adolescent and adult mice exposed to cocaine (or vehicle) pretreatment, either in an intermittent or "binge" (i.e., heavy cocaine use on a single occasion, which increases the likelihood of experiencing cocaine-related problems) fashion. Cocaine administration induced behavioral sensitization to a greater extent in adolescent than in adult mice. Cocaine-induced CPP was fairly similar in vehicle pretreated adolescent and adult mice, yet greater in adolescent vs. adults after cocaine-induced sensitization. The results confirmed the higher sensitivity of adolescent mice to cocaine-induced behavioral sensitization and suggest its association with greater sensitivity to cocaine's rewarding effects.
青少年对精神兴奋剂的神经和行为影响比成年人更为敏感，并且更容易滥用药物、产生依赖性或重新出现这些情况。我们曾报告过，与成年期预处理相比，青春期时的可卡因预处理更能促进行为敏化的表达。行为敏化与从药物使用到成瘾的转变有关，据推测它表明对药物的奖赏动机效应更为敏感。行为敏化与传统的药物奖赏测量方法（如条件性位置偏好，CPP）之间的关系尚未得到彻底研究，对于这种现象与年龄相关的差异知之甚少。本研究在接受可卡因（或载体）预处理的青少年和成年小鼠中测试了可卡因诱导的 CPP，预处理方式为间歇性或“狂欢”（即在一次狂饮中大量使用可卡因，增加了出现与可卡因相关问题的可能性）。与成年小鼠相比，可卡因在青少年小鼠中引起的行为敏化更为明显。在可卡因诱导的敏化后，接受可卡因预处理的青少年和成年小鼠之间的 CPP 差异不大，但在青少年与成年小鼠之间的差异较大。结果证实了青少年小鼠对可卡因诱导的行为敏化更为敏感，并表明其与对可卡因奖赏作用的敏感性增加有关。
