Effects of Sex, Estradiol, and Acute Stress on Spontaneous Recovery of a Conditioned Touchscreen Response in Rats

The present study examined sex differences and the effects of estradiol on acquisition and extinction using an appetitive reinforcement schedule in operant touchscreen chambers. Additionally, it aimed to clarify how acute stress influences response inhibition, as assessed by the spontaneous recovery of operant responses following extinction, in males, females, and ovariectomized females with and without estradiol treatment. In Experiment 1, male and female rats exhibited equal rates of acquisition. While male and female rats extinguished their response also at similar rates, female rats showed transient but significantly greater extinction compared to male rats during the first day of extinction. Acute stress administered immediately prior to the extinction retention test, conducted 21 days following extinction phase, enhanced spontaneous recovery of the learned response in both male and female rats, but also led to a more rapid decline in response rates across the re-extinction session. In Experiment 2, ovariectomized female rats receiving chronic estradiol or cholesterol (control) treatment showed no significant differences in acquisition or extinction learning. Unlike Experiment 1, both estradiol-treated and non-treated ovariectomized stressed rats exhibited lower spontaneous recovery throughout the extinction retention test, indicating that naturally cycling female hormones may modulate stress effects on response recovery. Additionally, non-stressed rats treated with estradiol demonstrated reduced responding in the early stages of the extinction retention test compared to controls. These findings suggest that acute stress enhances response recovery in intact, cycling female and male rats. However, in ovariectomized female rats, acute stress attenuates the spontaneous recovery of an extinguished response in a manner partially dependent on estradiol treatment. These results provide insight into how acute stress influences response inhibition in an appetitive learning paradigm and highlight the role of sex and gonadal hormone status in learning, memory, and response inhibition, with implications for stress-related disorders and addiction behavior.