Modulation of 8-OH-DPAT-induced hypothermia by imipramine in rats.
The effects of imipramine on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), the 5-hydroxytryptamine (5-HT)(1A)-receptor full agonist, -induced hypothermia was examined in rats. Single administration of imipramine (30 mg/kg, i.p.) attenuated 8-OH-DPAT-induced hypothermia. This effect of imipramine was blocked by the 5-HT(2A)-receptor antagonist ketanserin. 8-OH-DPAT-induced hypothermia was not altered 24 h after repeated administration of imipramine (1 - 10 mg/kg per day) for 14 days. However, 8-OH-DPAT-induced hypothermia was significantly enhanced in repeated imipramine (10 mg/kg per day)-treated rats that received 8-OH-DPAT plus imipramine 24 h after the final imipramine administration for 14 days. The 5-HT(2A)-receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)-DOI) attenuated the 8-OH-DPAT-induced hypothermia in drug naive rats. The inhibitory effect of (+/-)-DOI (0.3 mg/kg, s.c.) on 8-OH-DPAT-induced hypothermia was attenuated by repeated administration of imipramine (10 mg/kg per day) for 14 days. These findings suggest that enhancement of the 5-HT(1A) receptors by repeated administration of imipramine may be due to reduction of the inhibitory effects from the 5-HT(2A) receptors to the 5-HT(1A) receptors.
Kitamura
Yoshihisa
Y
Division of Pharmacy, Misasa Medical Center, Okayama University Medical School, Tottori, Japan. ykita@cc.okayama-u.ac.jp
Araki
Hiroaki
H
Shibata
Kazuhiko
K
Gomita
Yutaka
Y
Tanizaki
Yoshiro
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007035:Hypothermia / Q000139:chemically induced* / Q000378:metabolism; D007036:Hypothermia, Induced / Q000379:methods; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine