Targeting dopamine D2 receptors to alter fear extinction in adolescent rats

Anxiety disorders emerging in adolescence are especially challenging to treat, partly due to adolescents having poor extinction recall and high relapse rates following exposure therapy, relative to other ages. Despite its clear clinical significance, little work has examined treatments to enhance extinction in adolescence. Dopamine, a key neurotransmitter involved in learning and memory, plays a critical role in fear extinction in adults, but its role in extinction in adolescents has not been well-explored. In a series of experiments, we investigated the effects of sulpiride, a dopamine antagonist, on extinction recall in male and female adolescent rats. Animals underwent Pavlovian fear conditioning followed by extinction training the next day, where animals were injected with either sulpiride or saline 15 min prior. On the next day animals were tested for their extinction recall. Sulpiride-treated male adolescents exhibited impaired extinction recall (Experiment 1), while sulpiride enhanced extinction recall in female adolescents (Experiment 2). However, these results were not replicated in a follow-up experiment that also included a sulpiride-no extinction control group (Experiment 3). Further, in contrast to what has been reported in past studies with adults, we did not observe any effect of sulpiride on adult female and male extinction recall (Experiment 4). Overall, these findings suggest that sulpiride may have sex-specific effects on extinction recall in adolescence, as has been reported in adults, though these effects appear to not be robust. (PsycInfo Database Record (c) 2026 APA, all rights reserved).