Sex Differences in Conditioned Orienting and the Role of Estradiol in Addiction-Related Behaviors

Conditioned orienting response (OR) is a form of cue-directed behavior thought to indicate increased attentional and/or motivational processing of reward-associated stimuli. OR as a phenotype has been shown to predict both direct drug proclivity in female rats and behaviors indirectly related to drug proclivity in male rats, but no extant research has compared males and females in terms of their OR behavior or its notable substrates. As females are at increased risk for substance abuse, and the ovarian hormone estradiol is often cited as a driving factor for this predilection, it is important to characterize sex differences between males and females and explore what, if any, contribution estradiol has in behaviors which predict substance abuse. In these experiments, male and female rats [intact or ovariectomized (OVX) with/without estradiol replacement] were compared on a battery of behavioral tasks, including OR, novelty-seeking, attentional set-shifting, and ultrasonic vocalizations (USVs) to amphetamine treatment. Female rats, regardless of estradiol replacement, had higher OR scores than males. OR score was a predictor of attention impairments, and estradiol availability contributed to this relationship in females. Sex differences were not observed in novelty-seeking, attentional set-shifting, or USV response to amphetamine; however, estradiol replacement did alter the presentation of these behaviors.