Gauvin D V, Baird T J, Briscoe R J
Drug and Chemical Evaluation Section, Office of Diversion Control, Drug Enforcement Administration, Washington, DC 20537, USA.
Psychopharmacology (Berl). 2000 Sep;151(4):335-43. doi: 10.1007/s002130000477.
There at least two ways in which tolerance development to alcohol's behavioral effects could interact with its subsequent intake: 1) tolerance to alcohol's reward or reinforcing effects per se could lead to increased consumption, and 2) tolerance to alcohol's aversive effects could unmask alcohol's rewarding effects. These two mechanisms may differentially interact with preexisting genetic traits underlying alcoholism.
Alcohol's subjective attributes were assessed in selectively bred AA and ANA rats after the development of tolerance to alcohol's behaviorally disruptive effects on lever-press performance.
Rats were trained to press a lever under an FR30 schedule of food presentations. Group-dependent differential access to intoxicated practice, using a typical pre-post drug administration design, was utilized to promote the development of alcohol tolerance in only the group receiving intoxicated practice sessions. Subsequently, rats were trained to associate alcohol with unique place and taste stimuli in order to assess the relative changes in the approach towards, or avoidance of alcohol-related cues in each group.
Groups of AA and ANA rats given access to intoxicated practice demonstrated tolerance development. These groups subsequently conditioned place preferences and failed to develop conditioned taste aversions to alcohol. Passive alcohol exposure in the ANA rats set the occasion for the development of a place preference and delayed taste conditioning. AA rats exposed to passive alcohol exposure failed to condition place preferences and developed rapid taste aversions. Saline control rats failed to develop tolerance or place preferences but did condition a robust alcohol-induced taste aversion.
AA and ANA rats differ in their behavioral and pharmacokinetic response to chronic alcohol exposure. Compensatory responses interacting with approach-avoidance behaviors appear to be learned during intoxicated practice in the AA rats and during both intoxicated practice and passive exposure in the ANA rat line.
酒精行为效应耐受性的发展至少有两种方式可能与其后续摄入量相互作用:1)对酒精奖励或强化效应本身的耐受性可能导致饮酒量增加,2)对酒精厌恶效应的耐受性可能会揭示酒精的奖励效应。这两种机制可能与酒精中毒潜在的预先存在的遗传特征有不同的相互作用。
在对酒精对杠杆按压行为的干扰效应产生耐受性后,对选择性培育的AA和ANA大鼠的酒精主观属性进行评估。
训练大鼠在FR30食物呈现时间表下按压杠杆。采用典型的给药前后设计,根据组的不同,对醉酒练习的接触程度不同,仅在接受醉酒练习的组中促进酒精耐受性的发展。随后,训练大鼠将酒精与独特的位置和味道刺激联系起来,以评估每组对与酒精相关线索的接近或回避的相对变化。
获得醉酒练习的AA和ANA大鼠组表现出耐受性发展。这些组随后形成了条件性位置偏好,并且没有对酒精形成条件性味觉厌恶。ANA大鼠的被动酒精暴露为位置偏好的发展创造了条件,并延迟了味觉条件反射。暴露于被动酒精的AA大鼠没有形成位置偏好,而是迅速形成了味觉厌恶。生理盐水对照大鼠没有发展出耐受性或位置偏好,但确实形成了强烈的酒精诱导的味觉厌恶。
AA和ANA大鼠对慢性酒精暴露的行为和药代动力学反应不同。与接近-回避行为相互作用的补偿反应似乎是在AA大鼠的醉酒练习期间以及ANA大鼠系的醉酒练习和被动暴露期间习得的。