The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.
The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.
Osterlund
M K
MK
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, Karolinska Hospital, S-171 76, Stockholm, Sweden.
Overstreet
D H
DH
Hurd
Y L
YL
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000235:genetics*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D015347:RNA Probes; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011960:Receptors, Estrogen / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics*; D044263:Receptors, Serotonin, 5-HT1
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D015347:RNA Probes; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D011960:Receptors, Estrogen; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D004958:Estradiol