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KMID : 1009020190170030400
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Clinical Psychopharmacology and Neuroscience
2019 Volume.17 No. 3 p.400 ~ p.408
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Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats
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Choi Hyung-Jun
Im Soo-Jung
Park Hae-Ri
Park Su-Bin
Kim Chul-Eung
Ryu Seung-Hyong
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Abstract
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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.
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KEYWORD
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Aripiprazole, Adolescent, Cognition, Dopamine D2 receptors, Animal models
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