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 i nvestigated using a genetic animal model of depression, the Flinders Sensit ive 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-HT1A and 5-HT2A receptors were analyzed in several limbic-related are as of ovariectomized FSL and FRL rats treated with 17 beta-estradiol (0.15 mu g/g) or vehicle. The FSL animals were shown to express significantly low er levels of the 5-HT2A receptor transcripts in the perirhinal cortex, piri form cortex, and medial anterodorsal amygdala and higher levels in the CA 2 -3 region of the hippocampus. The only significant difference between the r at lines in ER mRNA expression was found in the medial posterodorsal amygda la, where the FSL rats showed lower ER alpha expression levels. Overall, es tradiol treatment increased 5-HT2A and decreased 5-HT1A receptor mRNA level s in several of the examined regions of both Lines. Thus, in many areas, es tradiol was found to regulate the 5-HT receptor mRNA expression in the oppo site direction to the alterations found in the FSL rats. These findings fur ther support the implication of 5-HT receptors, in particular the 5-HT2A su btype, in the etiology of affective disorders. Moreover, the ability of est radiol to regulate the expression of the 5-HT1A and 5-HT2A receptor genes m ight account for the reported influence of gonadal hormones in mood and dep ression. (C) 1999 Elsevier Science B.V. All rights reserved.