Long-term effects of aripiprazole treatment during adolescence on cognitive function and dopamine D2 receptor expression in neurodevelopmentally normal rats
Hyung Jun Choi 1, Soo Jung Im 1, Hae Ri Park 1, Subin Park 2, Chul-Eung Kim 3, Seunghyong Ryu 1*
1Department of Mental Health Research, National Center for Mental Health, Seoul, Republic of Korea, 2Department of Research Planning, National Center for Mental Health, Seoul, Republic of Korea, 3Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea
Received: May 2, 2018; Revised: August 2, 2018; Accepted: August 26, 2018; Published online: August 26, 2018.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, 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 significantly 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 risperidone-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 dopaminergic neurotransmission into early adulthood.
Keywords: Aripiprazole, Adolescence, Cognitive function, Dopamine D2 receptor, Animal model


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