Alcohol, place conditioning, and male rats: A systematic review for outcome prediction.

Abstract

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). To predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. Systematic review: structured search for relevant records in PUBMED and two other sources, eligible articles defined as those conforming to all inclusion criteria, selection of experiments failing all the exclusion criteria, and analysis of procedure-outcome relations according to the background of variables affecting associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre-exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict different rates of CPA and CPP: higher rates of CPA are predicted by single-housed, older, and heavier animals, while higher rates of CPP are predicted by group-housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, indicate the predictive analysis has broad consequences (from theoretical to translational ones) for PC in alcohol research, and specify variables needing more accurate investigation (rat sex, age, weight, strain, spatial configuration of the apparatus, and conditioning timetable). This review may improve our comprehension of results of alcohol-induced PC with rats, refining our understanding of the motivator function of alcohol and the alcohol-seeking behavior triggered by environmental contexts, and opening new research venues on their neurobiological basis.