Reversal of long-delay conditioned taste aversion learning in rats by sex hormone manipulation

Conditioned taste aversion (CTA) learning is an adaptive, robust, well-established learning and memory paradigm. Strong taste aversions develop to the conditioned stimulus (CS = saccharin) despite long delays between exposure to the CS and unconditioned stimulus (US = LiCl). Rats display a sexually dimorphic pattern of long-delay CTA learning (Foy et al., 1996). The present study examines whether this sex difference is a result of activational or organizational hormone action, because here we implanted gonadectomized rats with their normal hormone replacements, or with opposing hormones prior to testing in a 4-hr delayed CTA learning task. We found that gonadally intact male rats displayed a more robust CTA response than intact female rats. Gonadectomy essentially eliminated this sex difference; gonadectomized males and gonadectomized females displayed similar CTA responses. In gonadectomized rats, when their normal sex hormones were replaced with implanted hormone pellets, the sex difference in CTA learning was reinstated. In contrast, when gonadectomized rats were implanted with opposing hormones, the sex difference was reversed. Gonadectomized female rats implanted with 5alpha-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17beta-estradiol pellets. Regardless of the original developmental hormonal environment, our study suggests that an activational manipulation of circulating hormones serves to significantly influence long-delay CTA learning in rats.