High novelty-seeking predicts greater sensitivity to the conditioned rewarding effects of cocaine

Abstract

Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, identify “drug-vulnerable” individuals. The main objective of this work was to determine the capacity of two animal models—the novel object recognition task and the novel environment test—for evaluating to what extent novelty-seeking can predict greater sensitivity to the rewarding properties of cocaine in young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference, a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1mg/kg, i.p.). Three factors that predispose individuals to addiction were considered: age, sex and novelty-seeking trait. CPP was detected only in the young adults that spent most time exploring the novel environment (High Novel Environment Seekers, High-Environment-NS). The novel environment test seemed to be more effective than the novel object recognition task in identifying young adults vulnerable to drugs; specifically, it revealed a distinction between High- and Low-Environment-NS mice that predicted greater sensitivity to the rewarding properties of cocaine among young adults but not among adolescents. Although our results reveal a higher novelty preference among young adult females than among their male counterparts in the two NS tests, both sexes showed similar susceptibility to the rewarding effects of a sub-threshold dose of cocaine in the CPP. These findings suggest that screening can identify humans at-risk of becoming drug users, and may contribute to the development of prevention strategies based on specific vulnerabilities.