Alcohol, place conditioning, and male rats: A systematic review of 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). The aim of this systematic review was to predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. We sought relevant records in PUBMED and two other sources. Two reviewers independently assessed records for eligible articles (those meeting all inclusion criteria), selected alcohol-induced PC experiments (those meeting no exclusion criteria) from eligible articles, extracted data, and assessed the quality of included studies. We then conducted a predictive analysis of outcomes by examining procedure-outcome relations according to variables known to affect 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 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, discuss the broad theoretical and translational consequences of the predictive analysis for the use of PC in alcohol research, and specify variables needing more careful investigation. This review could improve our understanding of the results of alcohol-induced PC with rats, refine our understanding of the motivational function of alcohol and alcohol-seeking behavior triggered by environmental contexts, and open new avenues of research on their neurobiological basis.

Letter to the editor: A reply to Grahame (2023) commenting on “Alcohol, place conditioning, and male rats: A systematic review of outcome prediction”

“…Although we appreciate the commentary (Grahame, 2023) on our review (Marques et al, 2023), it surprised us because we did not expect a discussion stating that our work fails to provide predictive generalizations for humans. Reflecting on this, perhaps we did not emphasize enough the limitations in the literature of alcohol place conditioning (PC) for the fulfillment of this goal.…”

“…Considering all of this, in the first paragraphs of our review, we did not make a justification for alcohol PC. After indicating the relevant learned aspect of AUD to be modeled, we defined alcohol PC in a fit‐for‐purpose manner: to “(…) study the development of alcohol‐seeking and ‐craving behaviors triggered by cues, their repercussions over alcohol consumption, their genetic and neurobiological bases, and to test possible treatments” (Marques et al., 2023). From this definition, one can derive the use of PC to indirectly study alcohol's primarily rewarding or aversive effects that Grahame (2023) alluded to, and we cited in the second paragraph of our review.…”