Central dopaminergic actions of YM-14673, a new TRH analogue, in rodents

The effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on spontaneous movement, sniffing, climbing, licking, biting and circling behaviors were compared with those of TRH and methamphetamine, in rodents. YM-14673 in a dose of 1 mg/kg (i.p.) enhanced spontaneous motor activity in rats, and induced sniffing and climbing behaviors in mice. The licking and biting behaviors were not induced by administration of YM-14673 even in a high dose (30-100 mg/kg i.p.) to mice. In addition, ipsilateral circling did not follow the i.p. administration of YM-14673 in rats receiving cis-flupenthixol unilaterally into the striatum. YM-14673 was about 20-30 times more potent than TRH to induce sniffing and climbing behaviors and to increase spontaneous movement. The sniffing and climbing behaviors induced by administration of YM-14673 and TRH were antagonized by treatment with haloperidol and alpha-methyl-para-tyrosine (alpha-MT). Methamphetamine (0.5-10 mg/kg i.p.), unlike YM-14673, showed significant pharmacological effects in all behavioral experiments, so that the pharmacological profile of YM-14673 was different from that of methamphetamine. These results suggest that both YM-14673 and TRH induced behavioral changes, presumably due to facilitatory effects on the central dopaminergic system.