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.
Yamamoto
M
M
Central Research Laboratories, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan.
Ozawa
Y
Y
Sasamata
M
M
Koshikawa
N
N
Kobayashi
M
M
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D005475:Flupenthixol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019805:alpha-Methyltyrosine
D001384:Azetidines; D001385:Azetines; D004151:Dipeptides; D015259:Dopamine Agents; D008781:Methyltyrosines; D008694:Methamphetamine; D013973:Thyrotropin-Releasing Hormone; D019805:alpha-Methyltyrosine; C054995:azetirelin; D005475:Flupenthixol; D006220:Haloperidol; D001058:Apomorphine