Behavioural effects of shoaling on nicotine place preference in zebrafish

Nicotine activates the brain's reward systems leading to addiction. Zebrafish exhibit social behaviours, such as shoaling, making them an attractive model for investigating how social interactions influence behaviour. Here, we assessed the rewarding effects of nicotine on zebrafish shoaling behaviour, examined whether the shoal influences the rewarding properties of nicotine. To study shoaling behaviour under drug exposure, we compared nicotine at 15 and 50 mg/L as a reinforcer and a social stimulus through Pavlovian conditioning. Visual interaction of individual zebrafish with a shoal during conditioning or the CPP test was sufficient to decrease nicotine-CPP, spending more time closer to the shoal. We then examined the effect of the shoal during conditioning. When fish were conditioned as a group, 15 mg/L of nicotine induced a positive CPP, but 50 mg/L did not. No evidence of anxiety or stress was found. At 50 mg/L, the distance between zebrafish in the shoal increased, indicating a relaxed behaviour. To better characterize this effect, we exposed the fish to phenylbutyrate (PhB) (an HDAC inhibitor) known to reduce nicotine-CPP. In zebrafish conditioned in a shoal, 15 mg/L of nicotine inhibited CPP, but 50 mg/L did not, with reduced interfish distances. Our results indicate that the social environment, such as the presence of a shoal, can influence nicotine preference in zebrafish, which is significant for understanding social influences on addiction in vertebrates, including humans.