Understanding the role of environment in associative learning of nicotine-induced place preference conditioning in zebrafish

Environmental enrichment (EE) is a well-known strategy in animal behavior to improve the welfare and health of animals in captivity. EE provides animals with stimulating and engaging environments that promote natural behaviors, cognitive stimulation and stress reduction. EE turns out to be an important strategy to increase the validity and reproducibility of behavioral data. Zebrafish is a useful experimental model for pharmaceutical and toxicological screening to study mechanisms involved in behavioral flexibility. The present work examined for the first time whether exposure to an EE during conditioning in the conditioned place preference (EE-CPP) task modulates the rewarding properties of nicotine in zebrafish. Various combinations of preferred and avoided environments (via positive and aversive cues introduced in each compartment of the CPP tank) were tested in the EE-CPP task. Positive nicotine-CPP scores were obtained in all conditions tested, except when the aversive and preferred stimuli were placed in the same compartment. When two highly preferred stimuli (brown walls and plants) were associated with dots drawn on the floor of the nicotine-matched compartment, nicotine-CPP score was lower. These findings suggest that threatening stimuli in the environment where the drug is administered or consumed could disrupt conditioning and reduce drug rewarding effects. A series of other behavioral parameters corroborated EE-CPP scores. Our findings underscore the need for further research to better understand how these factors interact and influence an individual's vulnerability to nicotine addiction. The present study contributes to expand our understanding of the dynamics involved in the behavioral flexibility underlying nicotine addiction.