Progressive augmentation of locomotor activity in mice by long-term treatment with thyrotropin releasing hormone

The effect of daily administration of thyrotropin releasing hormone (TRH) on exploratory behavior (ambulation) was investigated in mice. TRH administered subcutaneously (2.5 and 10 mg/kg) exerted a biphasic action on locomotion, that is, an increase followed by a subsequent decrease. This TRH-induced hyperlocomotion was inhibited by a small dose of apomorphine (0.25 mg/kg, s.c.), a dopamine receptor agonist, but was conversely increased by a small dose of haloperidol (0.02 mg/kg, s.c.). Following administration of TRH (2.5 mg/kg, s.c.) for 21 successive days, the stimulatory effect on locomotion progressively increased whereas the inhibitory effect decreased, the hyperlocomotion continuing at a later period. At this time, the stimulatory effect of apomorphine (1 mg/kg, s.c.) on locomotion tended to decrease but that of methamphetamine (0.5 mg/kg, s.c.), a catecholamine releaser, was potentiated. The present results suggest that the long-term, daily administration of TRH enhances exploratory behavior of mice, presumably by increasing the synthesis and release of dopamine.