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 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.118.255380
4099  - http://jpet.aspetjournals.org/content/early/2019/07/15/jpet.118.255380.short
4100  - http://jpet.aspetjournals.org/content/early/2019/07/15/jpet.118.255380.full
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 non-pregnant 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 non-pregnant 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 pre-pregnancy levels soon following parturition. Similar to pregnant mice, 17β-estradiol replacement treatment in non-pregnant 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 transit 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 due to potential adverse effects to the fetuses.SIGNIFICANCE STATEMENT N/A