YM-14673, a thyrotropin-releasing hormone analogue, injected into the nucleus accumbens and the striatum produces repetitive jaw movements in rats.

Bilateral injections of the thyrotropin-releasing hormone (TRH) analogue, N alpha-[((S)-4-oxo-2-azetidinyl)-carbonyl]-L-histidyl-L-prolinamide dihydrate (YM-14673, 0.1 microgram and 1 microgram/0.2 microliters), into the nucleus accumbens, the dorsal and ventrolateral striatum produced repetitive jaw movements in a dose-dependent manner. The effects were greatest in the nucleus accumbens and smallest in the ventrolateral striatum. Pattern of the movements differed from that produced by injections of a mixture of SKF 38393 (5 micrograms) and quinpirole (10 micrograms); frequent tongue protrusions were evident in rats treated with the mixture but those were not seen in YM-14673-treated rats. TRH (1 microgram, 10 micrograms and 30 micrograms/0.2 microliters) did not evoke jaw movements from any of the sites. The non-selective dopamine receptor antagonist, cis-(Z)-flupentixol (10 micrograms), significantly reduced the response to administration of YM-14673 (1 microgram) into the nucleus accumbens or dorsal striatum, while the 5-hydroxytryptamine (5-HT)2A receptor antagonist, 2-(2-dimethylaminoethylthio)-3-phenylquinoline hydrochloride (ICI 169,369, 0.2 micrograms), did not affect the response to YM-14673 (1 microgram). Given intrathecally (0.5 microgram/5 microliters), both YM-14673 and TRH produced wet-dog shakes. Although the mechanisms giving rise to the display of jaw movements after intrastriatal injections of YM-14673 remain unknown, stimulation of the dopamine D1/D2 receptors may at least partly contribute to these effects. Anyhow, these mechanisms differ from that underlying the ability of YM-14673 and TRH to elicit wet-dog shakes, a mechanism that is known to involve serotonergic processes.