Increased DOI-induced wet-dog shakes in adrenocorticotropic hormone-treated rats are not affected by chronic imipramine treatment: possible involvement of enhanced 5-HT(2A)-receptor expression in the frontal cortex.
We examined the influence of imipramine, a traditional tricyclic antidepressant, on the binding to serotonin (5-HT)(2) receptors and levels of 5-HT(2A)-receptor mRNA in the frontal cortex of rats treated with adrenocorticotropic hormone (ACTH). Chronic treatment with ACTH significantly increased the binding of [(3)H]-ketanserin to 5-HT(2) receptors and the expression of 5-HT(2A)-receptor mRNA in the frontal cortex. However, it did not alter the concentration of 5-HT or 5-hydroxyindole acetic acid. The effect of chronic ACTH treatment on 5-HT(2) receptor and 5-HT(2A)-receptor mRNA levels was not altered by the chronic administration of imipramine. Also, imipramine did not affect the hyperfunction of 5-HT(2A) receptors caused by chronic ACTH treatment. These findings suggest that chronic treatment with ACTH acts to increase 5-HT(2A)-receptor synthesis through increased gene transcription, without modulating presynaptic serotonergic neurotransmission.
Kitamura
Yoshihisa
Y
Department of Pharmaceutical Care and Health Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. ykita@pheasant.pharm.okayama-u.ac.jp
Shibata
Kazuhiko
K
Akiyama
Kozue
K
Kimoto
Shizue
S
Fujitani
Yoshika
Y
Kitagawa
Kouhei
K
Kanzaki
Hirotaka
H
Ouchida
Mamoru
M
Shimizu
Kenji
K
Kawasaki
Hiromu
H
Sendo
Toshiaki
T
Gomita
Yutaka
Y
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000662:Amphetamines; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D015854:Up-Regulation
D000662:Amphetamines; D000929:Antidepressive Agents, Tricyclic; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000324:Adrenocorticotropic Hormone; D007650:Ketanserin; D007099:Imipramine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine