Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (II): Involvement of the DA system in the locomotor stimulating action of TA-0910.
The mechanism of the locomotor stimulating action of a new thyrotropin-releasing hormone (TRH) analog, TA-0910, was studied in rats. The locomotor stimulating action of TA-0910 (3 mg/kg) was inhibited by haloperidol or alpha-methyl-p-tyrosine (alpha-MT); slightly inhibited by phenoxybenzamine, prazosin, clonidine, or naloxone; not affected by propranolol, metergoline, or a low dose of scopolamine; and was enhanced by a high dose of scopolamine. The locomotor activity was increased by TA-0910 (0.3 mg/kg) in combination with methamphetamine, apomorphine, or L-DOPA under pretreatment with pargyline. A low dose of apomorphine inhibited the increase in locomotor activity induced by TA-0910 (3 mg/kg). The increase in locomotion was most notable and dose-dependent with the injection of 20 ng or more in the nucleus accumbens. The intravenous administration of TA-0910 produced dose-dependent and significant hyperlocomotion at 1 mg/kg or more. In the rats lesioned unilaterally in the nigrostriatal dopamine (DA) pathway by 6-hydroxydopamine, TA-0910 induced ipsilateral circling behavior at 3 mg/kg or more. This circling behavior was inhibited by haloperidol or alpha-MT. These results suggest that the locomotor stimulating action of TA-0910 is mediated primarily via the dopaminergic neuron, especially the nucleus accumbens of the mesolimbic DA system. Other possible mechanisms are also discussed.
Yamamura
M
M
Department of Pharmacology, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Kinoshita
K
K
Nakagawa
H
H
Ishida
R
R
D000818:Animals; D002404:Catheterization; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D006892:Hydroxydopamines; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
D006892:Hydroxydopamines; C065049:TA 0910; D013973:Thyrotropin-Releasing Hormone; D016627:Oxidopamine; D004298:Dopamine