Chronic treatment with the antidepressant amitriptyline decreases CRF-R1 receptor mRNA levels in the rat amygdala.
Using semi-quantitative in situ hybridization, corticotropin-releasing factor (CRF) and CRF receptor 1 (CRF-R1) mRNA levels were determined in the rat hypothalamus and amygdala after short-term (10 days) and chronic (4 weeks) treatment with the antidepressant amitriptyline. We found that chronic treatment with amitriptyline produced a significant decrease in CRF mRNA (to 33% of control) in the hypothalamic paraventricular nucleus (PVN). Short-term or chronic amitriptyline treatment had no effect on CRF-R1 mRNA levels in the PVN. However, after chronic treatment, there was a significant decrease of CRF-R1 mRNA levels in the lateral + basolateral (to 60% of control), and in the medial (to 70% of control) amygdala nuclei. These results suggest that the tricyclic antidepressant amitriptyline may exert part of its effects through modulation of hypothalamic CRF and of CRF-R1 gene expression in the amygdala.
Aubry
J M
JM
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA 92037, USA. jaubry@worldcom.ch
Pozzoli
G
G
Vale
W W
WW
D000639:Amitriptyline / Q000627:therapeutic use*; D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D017403:In Situ Hybridization; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000639:Amitriptyline