Place Conditioning: Agerelated Changes in the Rewarding and Aversive Effects of Alcohol.

Background: Alcohol abuse levels are very high in adolescents, creating a significant societal issue. It has been shown that people who begin alcohol use as adolescents are more likely to become addicts than people who initiate alcohol use as adults. It is important to note that the development of addiction in humans is more rapid with initiation in adolescence than in adulthood. Methods: To determine changes in the reinforcing efficacy of alcohol as a function of adolescent development, we used a place‐conditioning paradigm. In this study, we assessed the ability of ethanol to support a conditioned place preference (CPP) or aversion. Animals [postnatal days (PND) 25, 35, 45, and 60] were tested for alcohol‐induced conditioning in response to a range of ethanol doses (0.2, 0.5, 1.0, and 2.0 g/kg intraperitoneally) or saline. Results: In general, there was a trend for alcohol to produce an aversion to the ethanol‐paired compartment at higher doses. These patterns differed significantly as a function of age. Younger animals (PND 25) exhibited a CPP to a low dose and an aversion at high doses. Late‐adolescent (PND 45) animals exhibited a CPP at two moderate doses but a conditioned place aversion at the highest dose. PND 35 and 60 animals did not exhibit a CPP at any examined dose, and PND 60 animals exhibited a progressive aversion with increasing dose. Conclusions: The data show that the developmental processes of adolescence influence general responsiveness to alcohol. Specifically, late‐adolescent animals (PND 45) seem to prefer doses of alcohol that are either not reinforcing (0.5 g/kg) or are aversive (1.0 g/kg) at other ages. These processes need to be examined thoroughly to understand the development of addiction in adolescence. This is especially important given that alcohol abuse in adolescence may interfere with the usual pattern of brain development as it relates to alcohol reinforcement

High-novelty-preference rats are predisposed to compulsive cocaine self-administration.

IF : 6,99International audienceSensation/novelty-seeking is amongst the best markers of cocaine addiction in humans. However, its implication in the vulnerability to cocaine addiction is still a matter of debate, as it is unclear whether this trait precedes or follows the development of addiction. Sensation/novelty-seeking trait has been identified in rats on the basis of either novelty-induced locomotor activity (high-responder (HR) trait) or novelty-induced place preference (high-novelty-preference trait (HNP)). HR and HNP traits have been associated with differential sensitivity to psychostimulants. However, it has recently been demonstrated that HR rats do not develop compulsive cocaine self-administration (SA) after protracted exposure to the drug, thereby suggesting that at least one dimension of sensation/novelty seeking in the rat is dissociable from the vulnerability to switch from controlled to compulsive cocaine SA. We therefore investigated whether HNP, as measured as the propensity to choose a new environment in a free choice procedure, as opposed to novelty-induced locomotor activity, predicts the vulnerability to, and the severity of, addiction-like behavior for cocaine. For this, we identified HR/LR rats and HNP/LNP rats before any exposure to cocaine. After 60 days of cocaine SA, each rat was given an addiction score based on three addiction-like behaviors (persistence of responding when the drug is signaled as not available, high breakpoint under progressive ratio schedule and resistance to punishment) that resemble the clinical features of drug addiction, namely inability to refrain from drug seeking, high motivation for the drug and compulsive drug use despite adverse consequences. We show that, as opposed to HR rats, HNP rats represent a sub-population predisposed to compulsive cocaine intake, displaying higher addiction scores than LNP rats. This study thereby provides new insights into the factors predisposing to cocaine addiction, supporting the hypothesis that addiction is sustained by two vulnerable phenotypes: a 'drug use prone' phenotype such as HR which brings an individual to develop drug use and an 'addiction prone' phenotype, such as HNP, which facilitates the shift from sustained to compulsive drug intake and addiction