Ribeiro-Carvalho A, Lima C S, Medeiros A H, Siqueira N R, Filgueiras C C, Manhães A C, Abreu-Villaça Y
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 5 andar, Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
Neuroscience. 2009 Sep 15;162(4):1174-86. doi: 10.1016/j.neuroscience.2009.05.032. Epub 2009 May 22.
Relapse to drug use is a major public health problem. In this sense, understanding the biological substrates that are affected during withdrawal may provide information to prevent relapse. Both smoking and alcoholic beverage consumption usually begin during adolescence, however, little is known about the basic neurobiology of the combined adolescent exposure, particularly during withdrawal. Since nicotine is a cholinergic agonist and it has been shown that ethanol interferes with nicotinic acetylcholine receptors (nAChRs), the current study focused on the effects of drug withdrawal on the central cholinergic system. From the 30th to the 45th postnatal day (PN), C57BL/6 male and female mice were exposed to nicotine free base (NIC) and/or ethanol (ETOH). Four groups were analyzed: (1) concomitant NIC (50 microg/ml in 2% saccharin to drink) and ETOH (25%, 2 g/kg i.p. injected every other day) exposure; (2) NIC exposure; (3) ETOH exposure; (4) vehicle. We assessed nAChR binding, choline acetyltransferase (ChAT) activity and [(3)H]hemicholinium-3 (HC-3) binding in the cerebral cortex and midbrain of mice at short (PN50) and long term (PN75) withdrawal. NIC and NIC+ETOH promoted nAChR upregulation during a short-term withdrawal. NIC short-term withdrawal elicited an increase in ChAT activity that was reversed by ETOH withdrawal. In addition, NIC+ETOH elicited a decrease in ChAT activity at long term withdrawal. Regarding HC-3, ETOH and NIC+ETOH promoted a decrease that persisted at long-term withdrawal. The present study provides experimental evidence that nicotine and ethanol during adolescence interact resulting in cholinergic system alterations during withdrawal.
药物复吸是一个重大的公共卫生问题。从这个意义上讲，了解戒断期间受影响的生物学底物可能会为预防复吸提供信息。吸烟和酒精饮料消费通常始于青春期，然而，对于青少年联合接触（尤其是在戒断期间）的基础神经生物学知之甚少。由于尼古丁是一种胆碱能激动剂，并且已经表明乙醇会干扰烟碱型乙酰胆碱受体（nAChRs），因此本研究聚焦于药物戒断对中枢胆碱能系统的影响。从出生后第30天到第45天（PN），将C57BL/6雄性和雌性小鼠暴露于游离碱尼古丁（NIC）和/或乙醇（ETOH）。分析了四组：（1）同时接触NIC（在2%糖精中50微克/毫升以供饮用）和ETOH（25%，每隔一天腹腔注射2克/千克）；（2）接触NIC；（3）接触ETOH；（4）溶剂对照。我们评估了短期（PN50）和长期（PN75）戒断时小鼠大脑皮层和中脑中nAChR结合、胆碱乙酰转移酶（ChAT）活性以及[³H]半胱氨酸转运体-3（HC-3）结合情况。在短期戒断期间，NIC和NIC+ETOH促进了nAChR上调。NIC短期戒断引起ChAT活性增加，而ETOH戒断可逆转这一增加。此外，NIC+ETOH在长期戒断时引起ChAT活性降低。关于HC-3，ETOH和NIC+ETOH促进了其降低，且这种降低在长期戒断时持续存在。本研究提供了实验证据，表明青春期的尼古丁和乙醇相互作用，导致戒断期间胆碱能系统发生改变。
