Biphasic effects of thyrotropin-releasing hormone on exploratory behavior in mice

The neurological mechanism involved in biphasic effects of thyrotropin-releasing hormone (TRH) on exploratory behavior was studied in mice. Intraperitoneal injection of TRH (2.5 mg/kg) induced an increase of ambulation which was followed by subsequent decrease. Pretreatment with nialamide (20 mg/kg i.p.) potentiated the hyperactivity elicited by TRH but failed to affect the subsequent hypoactivity. Tetrabenazine (3 mg/kg i.p.) administered after nialamide markedly increased and sequentially decreased the ambulation, whereas tetrabenazine injected after TRH decreased ambulation as did tetrabenazine alone. TRH administered in combination with and tetrabenazine elicited a pronounced excitation followed by depression, as compared with those elicited by TRH alone or nialamide plus tetrabenazine. The results suggest that TRH induces a biphasic action in exploratory behavior and that this action may involve facilitation of dopamine release which results in an activation of post- and presynaptic dopamine receptors.