Effect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors.
The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 micrograms/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the Bmax values for 3H-ketanserin binding without any change in the Kd values. Moreover, this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (+/-)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (+/-)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropin-adrenal axis activation of rats increases both the number of 5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced by (+/-)DOI.
Kuroda
Y
Y
Division of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Mikuni
M
M
Ogawa
T
T
Takahashi
K
K
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D006213:Hallucinogens / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
D000662:Amphetamines; D006213:Hallucinogens; D011985:Receptors, Serotonin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000324:Adrenocorticotropic Hormone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D003345:Corticosterone