Sex dependent reduction by prenatal stress of the expression of 5HT1A receptors in the prefrontal cortex and CRF type 2 receptors in the raphe nucleus in rats: reversal by citalopram

Alterations in the serotonergic transmission and activity of corticotropin-releasing factor (CRF) family may underlie anxiety and depressive disorders. These could be corrected by treatment with SSRIs. The objective of the current study is to determine whether the increased anxiety of prenatally stressed (PS) rats of both sexes is associated with changes in 5HT1A and CRF type 2 receptors (5HT1AR and CRFR2) in the prefrontal cortex (PFC)-dorsal raphe nuclei (DRN) axis, and how these are affected by chronic treatment with citalopram (10 mg/kg/day). We focussed on GABAergic cells that co-express parvalbumin and/or neuropeptide Y, and 5HT1AR in the medial prefrontal cortex (mPFC) and on cells that express 5HT, parvalbumin, 5HT1AR or CRFR2 in the DRN. Immunohistochemistry with fluorescent antibodies demonstrated sex differences in the expression of 5HT1AR and CRFR2 protein. Prenatal stress selectively reduced the expression of 5HT1AR on GABAergic cells in the mPFC in males and that of CRFR2 in the DRN of females. Citalopram treatment for 5 weeks abolished the increase in anxiety in both sexes, restored the intensity of expression of 5HT1AR in the mPFC in males and increased their expression in the mPFC and DRN in females. Citalopram reduced CRFR2 expression in control and PS males but increased it in PS females. Male and female rats show differences in the expression of 5HT1AR and CRFR2 protein that are selectively reduced by prenatal stress. Reversal by citalopram of the changes in the expression of these receptors induced by prenatal stress support their role in the aetiology of anxiety.