Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats
10.9758/cpn.2019.17.3.400
- Author:
Hyung Jun CHOI
1
;
Soo Jung IM
;
Hae Ri PARK
;
Subin PARK
;
Chul Eung KIM
;
Seunghyong RYU
Author Information
1. Department of Mental Health Research, National Center for Mental Health, Seoul, Korea. seunghyongryu@gmail.com
- Publication Type:Original Article
- Keywords:
Aripiprazole;
Adolescent;
Cognition;
Dopamine D2 receptors;
Animal models
- MeSH:
Adolescent;
Adult;
Animals;
Anxiety;
Aripiprazole;
Blotting, Western;
Cognition;
Dopamine;
Hippocampus;
Humans;
Locomotion;
Male;
Memory, Short-Term;
Models, Animal;
Prefrontal Cortex;
Rats;
Rats, Sprague-Dawley;
Receptors, Dopamine D2;
Risperidone;
Synaptic Transmission;
Ventral Striatum
- From:Clinical Psychopharmacology and Neuroscience
2019;17(3):400-408
- CountryRepublic of Korea
-
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.
