Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo.
Adrenal corticosteroids bind to hippocampal glucocorticoid (GR) and mineralocorticoid receptors (MR), thereby affecting neurochemical transmission leading to altered mood, behaviour and neuroendocrine control. Serotoninergic (5-HT) and noradrenergic projections innervate the hippocampus, interacting with corticosteroid-sensitive cells. We have previously demonstrated that lesions of 5-HT neurons reduce hippocampal GR and MR mRNA levels and now examine whether acute or chronic treatment with antidepressant drugs, which potentiate endogenous monoamines by inhibiting their reuptake, affect hippocampal GR and MR mRNA expression in vivo. Rats were treated with amitriptyline (20 mg/kg.day-1), desipramine (10 mg/kg.day-1) or citalopram (20 mg/kg.day-1). After 2 or 14 days animals were killed, RNA extracted and GR and MR mRNA expression quantified by slot blot hybridization. Amitriptyline for 2 days led to a significant increase in MR (by 23 +/- 6%, compared with saline-treated controls), but not GR, mRNA expression. After 14 days amitriptyline, expression of both MR (87 +/- 27% rise) and GR mRNA (56 +/- 18% rise) had increased significantly in hippocampus, but not in parietal cortex. Desipramine for 14 days also increased MR (60 +/- 9%) and GR (42 +/- 9%) mRNA expression, though 14 days of citalopram altered only MR mRNA expression (17 +/- 5%). Thus, antidepressant drug administration elevates MR and GR mRNA expression in hippocampus, but not parietal cortex, in a time-dependent manner.
Seckl
J R
JR
Department of Medicine, Western General Hospital, Edinburgh, UK.
Fink
G
G
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008901:Mineralocorticoids; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000235:genetics; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000187:drug effects* / Q000235:genetics
D000928:Antidepressive Agents; D008901:Mineralocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid