Clin Psychopharmacol Neurosci.  2019 Aug;17(3):400-408. 10.9758/cpn.2019.17.3.400.

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

• Choi HJ
• Im SJ
• Park HR
• Park S
• Kim CE
• Ryu S

• KMID: 2457403
• DOI: http://doi.org/10.9758/cpn.2019.17.3.400

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.

Keyword

Aripiprazole; Adolescent; Cognition; Dopamine D2 receptors; Animal models

MeSH Terms

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
Aripiprazole
Dopamine
Receptors, Dopamine D2
Risperidone