Department of Physiology and Institute of Physiology and Biophysics (IFIBIO-Houssay, UBA-CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Department of Physiology and Institute of Physiology and Biophysics (IFIBIO-Houssay, UBA-CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jun 8;92:457-469. doi: 10.1016/j.pnpbp.2019.02.018. Epub 2019 Feb 28.
Sensitization of motor activity is a behavioural test to evaluate the effects of psychostimulants. Conditioned place preference (CPP) is an associative learning procedure to examine the rewarding properties of drugs. We aimed to assess whether motor sensitization to drugs of abuse can make zebrafish more vulnerable to establishing drug-induced CPP. We first evaluated sensitization of locomotor activity of zebrafish to repeated administrations of nicotine and cocaine during 5 days and after 5 days of withdrawal. After withdrawal, when zebrafish were re-exposed to the same dose of nicotine or cocaine locomotor activity was increased by 103% and 166%, respectively. Different groups of zebrafish were sensitized to nicotine or cocaine and trained on a nicotine-CPP task the day after withdrawal. The nicotine dose selected for sensitization was not effective for developing CPP in naïve zebrafish whereas it elicited CPP in zebrafish that were previously sensitized to nicotine or cocaine. Levels of nicotinic acetylcholine receptor β, α and α subunit, Pitx3, and tyrosine hydroxylase 1 (TH1) mRNAs were increased in the brain of nicotine- and cocaine-sensitized zebrafish. Nicotine-CPP performed with drug-sensitized zebrafish provoked further enhancements in the expression of α and α subunit, Pitx3, and TH1 mRNAs suggesting that the expression of these molecules in the reward pathway is involved in both processes. Our findings indicate that repeated exposures to low doses of drugs of abuse can increase subject's sensitivity to the rewarding properties of the same or different drugs. This further suggests that casual drug intake increases the probability of becoming addict.
运动活动敏化是一种行为测试，用于评估精神兴奋剂的作用。条件性位置偏好（CPP）是一种关联学习程序，用于检查药物的奖赏特性。我们旨在评估滥用药物的运动敏化是否会使斑马鱼更容易建立药物诱导的 CPP。我们首先评估了斑马鱼在 5 天内反复给予尼古丁和可卡因后运动活动的敏化作用，以及 5 天戒断后的反应。戒断后，当斑马鱼再次暴露于相同剂量的尼古丁或可卡因时，其运动活性分别增加了 103%和 166%。不同组的斑马鱼对尼古丁或可卡因进行了敏化，并在戒断后第二天进行了尼古丁-CPP 任务训练。用于敏化的尼古丁剂量对未敏化的斑马鱼没有产生 CPP 作用，但对先前敏化于尼古丁或可卡因的斑马鱼则诱发了 CPP。在尼古丁和可卡因敏化的斑马鱼的大脑中，烟碱型乙酰胆碱受体β、α 和 α 亚基、Pitx3 和酪氨酸羟化酶 1（TH1）mRNA 的水平增加。在使用药物敏化的斑马鱼进行尼古丁-CPP 后，α 和 α 亚基、Pitx3 和 TH1 mRNA 的表达进一步增强，这表明这些分子在奖赏途径中的表达参与了这两个过程。我们的研究结果表明，反复接触低剂量的滥用药物会增加个体对相同或不同药物的奖赏特性的敏感性。这进一步表明，偶然的药物摄入会增加成瘾的可能性。
