Role of serotonin in the regulation of beta-adrenoceptors by antidepressants.
The role of serotonin (5-HT) in the regulation of the beta-receptor density induced by long-term treatment with typical and atypical antidepressants was examined. Treatment with either mianserin (15 mg/kg, twice daily) or maprotiline (10 mg/kg, twice daily) for 7 days caused a significant decrease in the beta-receptor density, measured 6 h after the last dose, without a change in affinity. The reduction in beta-receptors disappeared rapidly (within 24 h). However, treatment with mianserin or maprotiline combined with fluoxetine, a selective 5-HT uptake inhibitor, significantly decreased the beta-receptor density even 24 h after the last dose. The combined administration of mianserin and 5-hydroxytryptophan (5-HTP) mimicked the effect of the combination with fluoxetine. Following pretreatment with p-chlorophenylalanine (PCPA) for 6 days, desipramine treatment for 3 days significantly decreased the beta-receptors 6 h after the last dose but this desipramine-induced decrease in beta-receptors was rapidly reversible (within 24 h). These results demonstrate that while intrasynaptic 5-HT levels are not a factor in the decrease in beta-receptors, they do play an important role in the preservation of the down-regulated state of the beta-receptor caused by antidepressants from rapid reversibility.
Asakura
M
M
Department of Neuropsychiatry, St. Marianna University School of Medicine, Kanagawa, Japan.
Tsukamoto
T
T
Kubota
H
H
Imafuku
J
J
Ino
M
M
Nishizaki
J
J
Sato
A
A
Shinbo
K
K
Hasegawa
K
K
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008376:Maprotiline / Q000494:pharmacology; D008566:Membranes / Q000187:drug effects; D008803:Mianserin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D005473:Fluoxetine; D008803:Mianserin; D008376:Maprotiline; D012701:Serotonin; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D003891:Desipramine