Effect of early-life stress or fluoxetine exposure on later-life conditioned taste aversion learning in Sprague-Dawley rats

Abstract

In rodents, early-life exposure to environmental stress or antidepressant medication treatment has been shown to induce similar long-term consequences on memory- and depression-related behavior in adulthood. To expand on this line of work, we evaluated how juvenile exposure to chronic variable stress (CVS) or the selective serotonin reuptake inhibitor fluoxetine (FLX) influences conditioned taste aversion (CTA) learning in adulthood. To do this, in Experiment 1, we examined how adolescent CVS alone (postnatal day [PND] 35-48), or with prenatal stress (PNS) history (PNS + CVS), influenced the acquisition and extinction of CTA in adult male Sprague Dawley rats. Specifically, at PND70+ (adulthood), rats were presented with 0.15 % saccharin followed by an intraperitoneal (i.p.) injection of lithium chloride (LiCl) to induce visceral malaise. A total of four saccharin (conditioned stimulus) and LiCl (unconditioned stimulus) pairings occurred across the CTA acquisition phase. Next, saccharin was presented without aversive consequences, and intake was measured across consecutive days of the extinction phase. No differences in body weight gain across the experimental days, rate of CTA acquisition, or extinction of CTA, were observed among the experimental groups (control, n = 7; CVS, n = 12; PNS + CVS, n = 9). In Experiment 2, we evaluated if early-life FLX exposure alters CTA learning in adulthood. Specifically, adolescent stress naïve male and female rats received FLX (0 or 20 mg/kg/i.p) once daily for 15 consecutive days (PND35-49). During antidepressant exposure, FLX decreased body weight gain in both male (n = 7) and female rats (n = 7), when compared to respective controls (male control, n = 8; female control, n = 8). However, juvenile FLX exposure decreased body weight-gain in adult male, but not female, rats. Lastly, adolescent FLX history had no effect on CTA acquisition or extinction in adulthood (PND70), in neither male nor female rats. Together, the data indicate that juvenile FLX exposure results in a long-term decrease of body weight-gain in a male-specific manner. Yet, independent of sex, neither early-life stress nor FLX exposure alters CTA learning in adulthood.

Keywords: Adolescence; CTA; Chronic variable stress; Hypophagia; Long-term; SSRI.

Fig. 1.

Mean ± SE body weight of prenatal stress and chronic variable stress (PNS+CVS; gray triangles), chronic variable stress (CVS; white triangles) and control rats (CON; circles).

Fig. 2.

Mean ± SE saccharin intake of prenatal stress and chronic variable stress (PNS+CVS; gray triangles), chronic variable stress (CVS; white triangles) and control rats (CON; circles) across 4 conditioning trials.

Fig. 3.

Mean ± SE saccharin intake of prenatal stress and chronic variable stress (PNS+CVS; gray triangles), chronic variable stress (CVS; white triangles) and control rats (CON; circles) across 20 extinction trials in which saccharin was presented without aversive consequence.

Fig. 4.

Change in body weight for controls (closed symbols) and fluoxetine-treated (open symbols) male (triangles) and female (circles) rats during fluoxetine treatment relative to body weight on PND35 in (A) male and (B) female groups. * denotes group differences that survived Bonferroni correction. FLX-treated groups gained weight significantly more slowly than their same-sex controls. Body weight across conditioned taste aversion testing (C) revealed FLX male (m) rats weighed significantly less than the CON male group but no group difference in females (f) was observed in adulthood.

Fig. 5.

Mean ± SE saccharin intake of control (closed symbols) and fluoxetine-treated (open symbols) males (triangles) and females (circles) across 4 conditioning trials.

Fig. 6.

Mean ± SE saccharin intake of control (closed symbols) and fluoxetine-treated (open symbols) males (triangles) and females (circles) across 20 extinction trials in which saccharin was presented without aversive consequence.