PT  - JOURNAL ARTICLE
AU  - Weibin Zha
AU  - Tao Hu
AU  - Mary F. Hebert
AU  - Joanne Wang
TI  - Effect of Pregnancy on Paroxetine-Induced Adiposity and Glucose Intolerance in Mice
AID  - 10.1124/jpet.118.255380
DP  - 2019 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 113--120
VI  - 371
IP  - 1
4099  - http://jpet.aspetjournals.org/content/371/1/113.short
4100  - http://jpet.aspetjournals.org/content/371/1/113.full
SO  - J Pharmacol Exp Ther2019 Oct 01; 371
AB  - Long-term use of selective serotonin reuptake inhibitors (SSRIs) targeting the serotonin transporter (SERT) has been suggested to be associated with an increased risk for obesity and type 2 diabetes. Previously, using a murine knockout model of SERT, we showed that estrogen suppression is involved in SERT deficiency–induced obesity and glucose intolerance in nonpregnant mice. The present study investigated the effects of chronic paroxetine treatment on adiposity and glucose tolerance in mice before and during pregnancy. Chronic paroxetine treatment in nonpregnant mice resulted in visceral adiposity and glucose intolerance accompanied by reduced circulating 17β-estradiol levels and ovarian expression of the aromatase (CYP19a1). Remarkably, pregnancy significantly reduced adiposity and improved glucose tolerance in paroxetine-treated mice by rebooting ovarian CYP19a1 expression and 17β-estradiol production. These effects appear to be reversible as ovarian CYP19a1 expression and circulating 17β-estradiol returned to prepregnancy levels soon after parturition. As in pregnant mice, 17β-estradiol replacement treatment in nonpregnant mice reduced paroxetine-induced adiposity. Our findings further suggested that modulation of estrogen synthesis underlies the observed metabolic adverse effects of SSRIs. Although our data revealed a transient reversal effect of pregnancy on SSRI-induced metabolic abnormalities, these observations are experimental and limited to mice. The use of SSRIs during human pregnancy should be cautioned because of potential adverse effects to the fetuses.