Alcohol-induced behavioral changes in zebrafish: The role of dopamine D2-like receptors

The dopaminergic system has been proposed to mediate alcohol-induced locomotor activity, yet the mechanisms underlying this behavioral response remain poorly understood. This study was conducted to investigate the role of dopamine D-2-like receptors in mediating alcohol-induced behavioral responses. In experiment 1, we examined the effects of high concentrations (0, 2.5, 5, 10 mu M) of haloperidol on motor responses. In experiment 2, we examined the effects of low concentrations (0, 0.625, 1.25, 2.5 mu M) of haloperidol on anxiety-like behavioral responses using the novel tank test. In experiment 3, we examined the effect of pre-treating zebrafish with different concentrations of haloperidol (0, 0.625, 2.5 mu M) and subsequently exposing them to 0 or 1 % alcohol. In experiment 1, haloperidol induced an inverted U-shaped concentration-dependent increase in locomotor activity. In experiment 2, haloperidol (2.5 mu M) reduced the absolute turn angle and freezing behavior in a new environment. In experiment 3, acute alcohol exposure significantly increased locomotor activity and decreased anxiety-like behavioral responses. Pre-treating zebrafish with the lower dose of haloperidol (0.625 mu M) abolished the alcohol-induced locomotor activity, without altering anxiety-like behavioral responses. However, pre-treating with the higher dose of haloperidol (2.5 mu M) abolished both alcohol-induced increase of locomotor activity and reduction of anxiety-like behavioral responses. The results suggest alcohol-induced locomotor hyperactivity in zebrafish is mediated via activation of dopamine D-2-like receptors, whereas anxiety-like behavioral responses may only be altered by a high haloperidol concentration, at which dose the drug may affect receptors other than D-2-R.