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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Neuronal nicotinic receptor ligands modulate chronic nicotine-induced ethanol consumption in C57BL/6J mice
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Neuronal nicotinic receptor ligands modulate chronic nicotine-induced ethanol consumption in C57BL/6J mice

机译：神经元烟碱样受体配体调节C57BL / 6J小鼠中慢性尼古丁诱导的乙醇消耗

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摘要

Alcohol and nicotine are commonly abused drugs in humans and evidence suggests that neuronal nicotinic acetylcholine receptors (nAChRs) in the midbrain dopamine system are common targets for the neurobehavioral interactions between alcohol (ethanol) and nicotine. The present study examined the efficacy of nAChR ligands with different pharmacological profiles such as cytisine, lobeline and dihydro-β-erythroidine (DHβE) to modulate chronic nicotine-induced increase in ethanol intake by C57BL/6J mice, using a two-bottle choice procedure. After establishment of baseline ethanol preference (10%, v/v), animals received daily subcutaneous injections of saline, nicotine (0.4 mg/kg) or different doses of cytisine, lobeline or DHβE 15 min prior to nicotine, for 10 days. Ethanol and water were presented immediately after the last (saline or nicotine) injection and fluid levels were monitored for post 1 h and 2 h treatment. Compared to control, nicotine injection significantly increased mean ethanol intake over 10 days, at both post 1 h and 2 h. Pretreatment with cytisine (0.5, 1.5 or 3.0 mg/kg) or lobeline (4.0 or 10.0 mg/kg) significantly reduced nicotine-induced increase in ethanol intake post 1 h and 2 h, without affecting water consumption. DHβE (0.5 or 2.0 mg/kg) failed to suppress nicotine-induced ethanol intake across 2 h post injection. These results indicate that nAChR-mediated signaling is critical in regulating nicotine-induced ethanol drinking behaviors.
机译：酒精和尼古丁是人类中经常滥用的药物，证据表明，中脑多巴胺系统中的神经元烟碱乙酰胆碱受体（nAChRs）是酒精（乙醇）与尼古丁之间神经行为相互作用的常见靶标。本研究使用两瓶选择程序检查了具有不同药理学特征的nAChR配体（如胱氨酸，肝胆碱和二氢-β-类红血球素（DHβE））对C57BL / 6J小鼠调节慢性尼古丁诱导的乙醇摄入增加的功效。 。在建立基线乙醇偏爱（10％，v / v）后，动物在尼古丁前15分钟每天皮下注射生理盐水，尼古丁（0.4 mg / kg）或不同剂量的胱氨酸，肝素或DHβE，持续10天。在最后一次注射（盐水或尼古丁）后立即提供乙醇和水，并在治疗1小时和2小时后监测体液水平。与对照相比，在1小时和2小时后的10天内，尼古丁注射液显着增加了平均乙醇摄入量。用半胱氨酸（0.5、1.5或3.0 mg / kg）或肝胆碱（4.0或10.0 mg / kg）进行预处理可显着降低烟碱诱导的1小时和2小时后乙醇摄入量的增加，而不会影响用水量。 DHβE（0.5或2.0 mg / kg）在注射后2小时内未能抑制尼古丁诱导的乙醇摄入。这些结果表明，nAChR介导的信号传导在调节尼古丁诱导的乙醇饮酒行为中至关重要。

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