YM-14673, A THYROTROPIN-RELEASING-HORMONE ANALOG, INJECTED INTO THE NUCLEUS-ACCUMBENS AND THE STRIATUM PRODUCES REPETITIVE JAW MOVEMENTS INRATS

Bilateral injections of the thyrotropin-releasing hormone (TRH) analog ue, o-2-azetidinyl}-carbonyl]-L-histidyl-L-prolinamide dihydrate (YM-1 4673, 0.1 mu g and 1 mu g/0.2 mu l), into the nucleus accumbens, the d orsal and ventrolateral striatum produced repetitive jaw movements in a dose-dependent manner. The effects were greatest in the nucleus accu mbens and smallest in the ventrolateral striatum. Pattern of the movem ents differed from that produced by injections of a mixture of SKF 383 93 (5 mu g) and quinpirole (10 mu g); frequent tongue protrusions were evident in rats treated with the mixture but those were not seen in Y M-14673-treated rats. TRH (1 mu g, 10 mu g and 30 mu g/0.2 mu l) did n ot evoke jaw movements from any of the sites. The non-selective dopami ne receptor antagonist, cis-(Z)-flupentixol (10 mu g), significantly r educed the response to administration of YM-14673 (1 mu g) into the nu cleus accumbens or dorsal striatum, while the 5-hydroxytryptamine (5-H T)(2A) receptor antagonist, 2-(2-dimethylaminoethylthio)-3-phenylquino line hydrochloride (ICI 169,369, 0.2 mu g), did not affect the respons e to YM-14673 (1 mu g). Given intrathecally (0.5 mu g/5 mu l), both YM -14673 and TRH produced wet-dog shakes. Although the mechanisms giving rise to the display of jaw movements after intrastriatal injections o f YM-14673 remain unknown, stimulation of the dopamine D-1/D-2 recepto rs may at least partly contribute to these effects. Anyhow, these mech anisms differ from that underlying the ability of YM-14673 and TRH to elicit wet-dog shakes, a mechanism that is known to involve serotonerg ic processes.