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

RATIONALE: The dopaminergic system has been proposed to mediate alcohol-induced locomotor activity, yet the mechanisms underlying this behavioral response remain poorly understood.

OBJECTIVES

This study was conducted to investigate the role of dopamine D2-like receptors in mediating alcohol-induced behavioral responses.

METHODS

In experiment 1, we examined the effects of high concentrations (0, 2.5, 5, 10 μM) of haloperidol on motor responses. In experiment 2, we examined the effects of low concentrations (0, 0.625, 1.25, 2.5 μM) 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 μM) and subsequently exposing them to 0 or 1 % alcohol.

RESULTS

In experiment 1, haloperidol induced an inverted U-shaped concentration-dependent increase in locomotor activity. In experiment 2, haloperidol (2.5 μM) 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 μM) abolished the alcohol-induced locomotor activity, without altering anxiety-like behavioral responses. However, pre-treating with the higher dose of haloperidol (2.5 μM) abolished both alcohol-induced increase of locomotor activity and reduction of anxiety-like behavioral responses.

CONCLUSION

The results suggest alcohol-induced locomotor hyperactivity in zebrafish is mediated via activation of dopamine D2-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 D2-R.