Open AccessMice overexpressing CRH show reduced responsiveness in plasma corticosterone after a 5‐HT 1A receptor challenge
Author(s) -
Van Gaalen M. M.,
Reul J. H. M.,
Gesing A.,
StenzelPoore M. P.,
Holsboer F.,
Steckler T.
Publication year - 2002
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1034/j.1601-183x.2002.10305.x
Subject(s) - endocrinology , medicine , corticosterone , serotonergic , 5 ht1a receptor , serotonin , agonist , receptor , neurotransmitter , autoreceptor , 5 ht receptor , hormone , chemistry , biology
Corticotropin‐releasing hormone (CRH) overproduction and serotonergic dysfunction have both been implicated in a range of psychiatric disorders, such as anxiety and depression, and several studies have shown interactions between these two neurotransmitter systems. In this study, we investigated the effects of CRH challenge on hypothalamo‐pituitary‐adrenal (HPA) axis activity in female transgenic mice overproducing CRH. Furthermore, the effects of mild stress on HPA axis activity and body temperature were investigated in these mice. Pre‐ and post‐synaptic 5‐HT 1A receptor function were studied by monitoring body temperature and plasma corticosterone levels after challenge with the 5‐HT 1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propyl‐amino)‐tetralin (8‐OH‐DPAT). Hypothermia in response to 8‐OH‐DPAT treatment did not differ between transgenic and wild type mice, indicating unaltered somatodendritic 5‐HT 1A autoreceptor function in mice overproducing CRH. In wild type mice 8‐OH‐DPAT increased plasma corticosterone levels, but not in transgenic animals. CRH injection, however, increased corticosterone levels in both groups. These data suggest desensitization of post‐synaptic, but not pre‐synaptic, 5‐HT 1A receptors in mice overproducing CRH. These findings resemble those seen in depressed patients following 5‐HT 1A challenge, which is in accord with the hypothesized role of CRH in the pathogenesis of depression.