Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats

Objective: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behav-ior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. Methods: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36‒56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71‒84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. Results: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed sig-nificantly among the 3 groups ( F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group ( post-hoc test p = 0.013). D2R levels in the medial PFC ( F = 8.72, p = 0.001) and hippocampus ( F = 13.54, p ＜ 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risper-idone-treated rats ( post-hoc test p = 0.025 and p ＜ 0.001, respectively) and controls ( post-hoc test p ＜ 0.001, all). Conclusion: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dop-aminergic neurotransmission into early adulthood.