Site-specific regulation of corticosteroid and serotonin receptor subtype gene expression in the rat hippocampus following 3,4-methylenedioxymethamphetamine: role of corticosterone and serotonin.
Abnormal interactions between serotonin (5-hydroxytryptamine) and glucocorticoids, notably in the hippocampus, may underpin neuroendocrine, affective and cognitive dysfunction in depression and ageing. Glucocorticoids act via intracellular glucocorticoid and mineralocorticoid receptors, whereas 5-hydroxytryptamine binds to a family of transmembrane sites; both cross- and auto-regulation have been proposed. To determine the roles of 5-hydroxytryptamine and corticosterone in the short-term control of hippocampal receptor gene expression, we used 3,4-methylenedioxymethamphetamine (20 mg/kg), which causes acute release of both 5-hydroxytryptamine and corticosterone. 3,4-methylenedioxymethamphetamine increased mineralocorticoid receptor messenger RNA expression throughout the hippocampus after 16 h. In rats with fixed glucocorticoid levels (adrenalectomy plus corticosterone pellets) this effect was lost in CA1-4, suggesting corticosterone-mediation, but maintained in the dentate gyrus, indicating 5-hydroxytryptamine involvement. In contrast, 3,4-methylenedioxymethamphetamine decreased glucocorticoid receptor messenger RNA expression in the dentate gyrus and CA1 within 4 h, but only in adrenal-intact rats, suggesting corticosterone control. 5-Hydroxytryptamine1A receptor messenger RNA expression was decreased in CA1 in both groups of rats, but increased in the dentate gyrus only in corticosterone-fixed rats, suggesting 5-hydroxytryptamine differentially regulates expression of this gene within hippocampal subfields. 5-hydroxytryptamine2C receptor messenger RNA was decreased in ventral CA1 only in adrenal-intact rats, suggesting a corticosterone effect, and decreased in the subiculum in both groups, indicating 5-hydroxytryptamine mediation. These results show the complexity and intricate subregional-specificity of 5-hydroxytryptamine and corticosterone interactions upon hippocampal corticosteroid and 5-hydroxytryptamine receptor gene expression. 3,4-Methylenedioxymethamphetamine-induced alterations in hippocampal receptor gene expression may play a role in the mood and behavioural changes associated with this drug of abuse.
Yau
J L
JL
University of Edinburgh, Department of Medicine, Western General Hospital, U.K.
Noble
J
J
Seckl
J R
JR
D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology*
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D011985:Receptors, Serotonin; D011987:Receptors, Steroid; D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003345:Corticosterone