Effects of putative dopamine D3 receptor agonists, 7-OH-DPAT, and quinpirole, on yawning, stereotypy, and body temperature in rats.
7-OH-DPAT ((+/-)-2-(dipropylamino)-7-hydroxy-1,2,3,4-tetrahydronaphthalene) was recently identified as a dopamine receptor agonist having a > 100-, 1,000- and > 10,000-fold higher affinity for dopamine D3 than for D2, D4 and D1 receptors, respectively. Quinpirole (LY 171555) has also been reported to have a 113-fold greater affinity for dopamine D3 receptors than for D2 receptors. Therefore, we investigated the effects of these putative dopamine D3 receptor agonists on yawning, stereotypy and rectal temperature in rats (N = 424). 7-OH-DPAT and quinpirole administered subcutaneously (SC) at respective low doses of 10-250 micrograms/kg and 25-500 micrograms/kg elicited yawning behavior. The yawning induced by these agents was blocked by spiperone (0.5 mg/kg, SC) and scopolamine (0.5 mg/kg, SC) but was increased by intraperitoneal (IP) administration of pindolol (20 mg/kg). The yawning was also potentiated after treatment with reserpine. 7-OH-DPAT and quinpirole at respective high doses of 0.25 mg/kg (SC) and 0.5 mg/kg (SC) evoked slight stereotypy such as sniffing and licking, and this effect was enhanced by a selective dopamine D1 receptor agonist, SK&F 38393 (1-phenyl-2,3,4,5,-tetrahydro-(1H)-3-benzazepine-7,8-diol). 7-OH-DPAT (0.5 mg/kg, SC) and quinpirole (0.5 mg/kg, SC) decreased, but SK&F 38393 (10 mg/kg, SC) increased body temperature. However, the hyperthermia induced by SK&F 38393 was interestingly enhanced by 7-OH-DPAT and quinpirole.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan.
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M
Kurashima
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Yamada
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M
Nagashima
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K
Shirakawa
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T
Furukawa
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3; D013239:Stereotyped Behavior / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects*
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D004873:Ergolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin