Gulick Danielle, Gould Thomas J
Department of Psychology, Neuroscience Program, Temple University, Philadelphia, PA 19122, USA.
Psychopharmacology (Berl). 2008 Feb;196(3):483-95. doi: 10.1007/s00213-007-0982-x. Epub 2007 Oct 30.
Alcohol and nicotine are commonly co-abused; one possible explanation for co-abuse is that each drug ameliorates the aversive effects of the other. Both drugs have dose-dependent effects on learning and memory. Thus, this study examined the interactive effects of acute ethanol and acute, chronic, or withdrawal from chronic nicotine on fear conditioning in C57BL/6J mice.
Conditioning consisted of auditory conditioned stimulus-foot-shock unconditioned stimulus pairings. For acute studies, saline or ethanol, then saline or nicotine was administered before training, and saline or nicotine was also administered before testing. For chronic and withdrawal studies, saline or nicotine was administered chronically, and ethanol or saline was administered before training.
Acute nicotine (0.09 mg/kg) reversed ethanol-induced deficits (1.0 and 1.5 g/kg) in contextual and cued fear conditioning, whereas a low dose of ethanol (0.25 g/kg) reversed nicotine (6.3 mg kg(-1) day(-1)) withdrawal-induced deficits in contextual conditioning. Tolerance developed for the effects of nicotine on ethanol-induced deficits in conditioning and cross-tolerance between chronic nicotine and acute ethanol was seen for the enhancing effects of ethanol on conditioning.
The complex and sometimes polar actions of ethanol and nicotine on behavior may contribute to co-abuse of these drugs. Specifically, smoking may initially reduce the aversive effects of ethanol, but tolerance develops for this effect. In addition, low doses of alcohol may lessen nicotine withdrawal symptoms.
酒精和尼古丁常常被共同滥用;共同滥用的一种可能解释是,每种药物都能减轻另一种药物的厌恶作用。两种药物对学习和记忆都有剂量依赖性影响。因此,本研究考察了急性乙醇与急性、慢性尼古丁或慢性尼古丁戒断对C57BL/6J小鼠恐惧条件反射的交互作用。
条件反射由听觉条件刺激-足部电击非条件刺激配对组成。在急性研究中,在训练前给予生理盐水或乙醇,然后给予生理盐水或尼古丁,在测试前也给予生理盐水或尼古丁。在慢性和戒断研究中,长期给予生理盐水或尼古丁,在训练前给予乙醇或生理盐水。
急性尼古丁(0.09毫克/千克)逆转了乙醇诱导的(1.0和1.5克/千克)情境性和线索性恐惧条件反射缺陷,而低剂量乙醇(0.25克/千克)逆转了尼古丁(6.3毫克·千克⁻¹·天⁻¹)戒断诱导的情境性条件反射缺陷。尼古丁对乙醇诱导的条件反射缺陷的作用产生了耐受性,并且在乙醇对条件反射的增强作用方面,观察到慢性尼古丁和急性乙醇之间存在交叉耐受性。
乙醇和尼古丁对行为的复杂且有时相反的作用可能导致这些药物的共同滥用。具体而言,吸烟最初可能会减轻乙醇的厌恶作用,但这种作用会产生耐受性。此外,低剂量酒精可能会减轻尼古丁戒断症状。