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.
Miwa
Y
Y
Department of Pharmacology, Nihon University School of Dentistry, Tokyo, Japan.
Koshikawa
N
N
Miyata
N
N
Koshida
Y
Y
Kobayashi
M
M
Cools
A R
AR
D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005475:Flupenthixol / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D007568:Jaw / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D001384:Azetidines; D004151:Dipeptides; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D005475:Flupenthixol