[TRH and its analog (DN-1417). Effects on central dopaminergic system-dependent behaviors in rats and mice]

Effects of TRH and its analog, gamma-butyrolactone-gamma-carbonyl-histidyl-prolinamide citrate (DN-1417), on circling, stereotyped or climbing behavior were investigated in rats and mice. High doses of TRH (100 mg/kg, i.p.) and DN-1417 (20-50 mg/kg, i.p.) produced a significant ipsilateral circling behavior in rats with the lesions of the unilateral dopamine (DA) pathway by 6-hydroxydopamine. In intact mice, stereotyped sniffing accompanying hyperactivity was caused at low doses of TRH or DN-1417 (1-20 mg/kg, i.p.), and stereotyped licking behavior was observed at high doses of TRH or DN-1417 (20-200 mg/kg, i.p.). Furthermore, TRH, DN-1417 or methamphetamine caused a dose-related climbing behavior in mice pretreated with L-DOPA and Ro 4-4602. Circling behavior, stereotyped sniffing or licking behavior induced by TRH or DN-1417 was markedly suppressed by pretreatment with pimozide or alpha-methyltyrosine. However, atropine and scopolamine potentiated the circling inducing action of TRH or DN-1417, in contrast with suppression of the licking behavior. These results suggest that TRH and DN-1417 produce circling, sniffing, licking and climbing behaviors via activation of the central DA system, and that cholinergic mechanisms may be also involved in licking behavior induced by TRH or DN-1417.