Modulation of social preference and avoidance of zebrafish conspecifics treated with selected neuroactive compounds

Social interaction and preference are essential parts of human and animal behavior. Zebrafish are rapidly emerging as a major model organism in neurobehavioral research and, as highly social animals, enable probing of their social preference and its pharmacological modulation. Neuroactive drug effects, however, can also be socially transmittable, thereby indirectly affecting drug-free animal behavior as well. Here, we examine this possibility in adult zebrafish by assessing their social preference for conspecifics treated using a wide range of neuroactive drugs with well established effects in zebrafish. Zebrafish were treated with acute or chronic neuroactive drugs (GBR-12909, fluoxetine, reserpine, caffeine, arecoline, nicotine, cuprizone, ethanol, and atropine), and exposed to target fish in the three-chamber social preference test, scoring time the latter spent in each zone. Overall, we found their overt social preference for conspecifics treated with acute nicotine and GBR-12909, and social avoidance of fish exposed to all other drugs used, except cuprizone and ethanol. These findings confirm altered social preference for central nervous system (CNS) drug-treated zebrafish, but suggest that this preference is nonlinear and does not correlate with anxiolytic or anxiogenic drug profiles. Further research is needed to explore why some CNS drug-evoked behavioral effects render conspecifics socially attractive or aversive to observer zebrafish, and to determine potential practical and translational implications of these findings for neuropharmacology and biological psychiatry.