TY - JOUR
TI - 5-HT1A, 5-HT2A, and 5-HT2C receptor mRNA modulation by antidepressant treatment in the chronic mild stress model of depression: Sex differences exposed
AU - Pitychoutis, P.M.
AU - Dalla, C.
AU - Sideris, A.C.
AU - Tsonis, P.A.
AU - Papadopoulou-Daifoti, Z.
JO - AIMS Neuroscience
PY - 2012
VL - 210
TODO - null
SP - 152-167
PB - 
SN - null
TODO - 10.1016/j.neuroscience.2012.03.003
TODO - clomipramine;  messenger RNA;  serotonin 1A receptor;  serotonin 2A receptor;  serotonin 2C receptor, animal experiment;  animal model;  animal tissue;  article;  chronic mild stress;  chronic stress;  controlled study;  dentate hilus;  depression;  disease model;  female;  gene expression;  hippocampal CA1 region;  hippocampal CA3 region;  histochemistry;  in situ hybridization;  male;  nonhuman;  orbital cortex;  priority journal;  rat;  sex difference, Animals;  Antidepressive Agents, Tricyclic;  Brain;  Clomipramine;  Depression;  Disease Models, Animal;  Female;  In Situ Hybridization;  Male;  Rats;  Rats, Sprague-Dawley;  Receptors, Serotonin;  RNA, Messenger;  Sex Characteristics;  Stress, Psychological
TODO - It is well established that women experience major depression at roughly twice the rate of men. Interestingly, accumulating clinical and experimental evidence shows that the responsiveness of males and females to antidepressant pharmacotherapy, and particularly to tricyclic antidepressants (TCAs), is sex-differentiated. Herein, we investigated whether exposure of male and female rats to the chronic mild stress (CMS) model of depression, as well as treatment with the TCA clomipramine may affect serotonergic receptors' (5-HTRs) mRNA expression in a sex-dependent manner. Male and female rats were subjected to CMS for 4 weeks and during the next 4 weeks they concurrently received clomipramine treatment (10 mg/ml/kg). CMS and clomipramine's effects on 5-HT1AR, 5-HT2AR, and 5-HT2CR mRNA expression were assessed by in situ hybridization histochemistry in selected subfields of the hippocampus and in the lateral orbitofrontal cortex (OFC), two regions implicated in the pathophysiology of major depression. CMS and clomipramine treatment induced sex-differentiated effects on rats' hedonic status and enhanced 5-HT1AR mRNA expression in the cornu ammonis 1 (CA1) hippocampal region of male rats. Additionally, CMS attenuated 5-HT1AR mRNA expression in the OFC of male rats and clomipramine reversed this effect. Moreover, 5-HT2AR mRNA levels in the OFC were enhanced in females but decreased in males, while clomipramine reversed this effect only in females. CMS increased 5-HT2CR mRNA expression in the CA4 region of both sexes and this effect was attenuated by clomipramine. Present data exposed that both CMS and clomipramine treatment may induce sex-differentiated and region-distinctive effects on 5-HTRs mRNA expression and further implicate the serotonergic system in the manifestation of sexually dimorphic neurobehavioral responses to stress. © 2012 IBRO.
ER -