Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats
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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.
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.
참고문헌 (38)
- Olfson M, "National trends in the office-based treatment of children, adolescents, and adults with antipsychotics", Arch Gen Psychiatry, 69, pp.1247~1256 (2012)
- Olfson M, "Treatment of young people with antipsychotic medications in the United States", JAMA Psychiatry, 72, pp.867~874 (2015)
- Correll CU, "Developments in pediatric psychopharmacology : focus on stimulants, antidepressants, and antipsychotics", J Clin Psychiatry, 72, pp.655~670 (2011)
- Correll CU, "Antipsychotic use in youth without psychosis : a double-edged sword", JAMA Psychiatry, 72, pp.859~860 (2015)
- Bardgett ME, "Adult rats treated with risperidone during development are hyperactive", Exp Clin Psychopharmacol, 21, pp.259~267 (2013)
- Vinish M, "Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function", Int J Neuropsychopharmacol, 16, pp.1599~1609 (2013)
- Milstein JA, "Olanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and function", PLoS One, 8, pp.e57308~ (2013)
- Moran-Gates T, "Effects of risperidone on dopamine receptor subtypes in developing rat brain", Eur Neuropsychopharmacol, 17, pp.448~455 (2007)
- Xu S, "Olanzapine antipsychotic treatment of adolescent rats causes long term changes in glutamate and GABA levels in the nucleus accumbens", Schizophr Res, 161, pp.452~457 (2015)
- Burris KD, "Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors", J Pharmacol Exp Ther, 302, pp.381~389 (2002)
- Kirino E, "Efficacy and safety of aripiprazole in child and adolescent patients", Eur Child Adolesc Psychiatry, 21, pp.361~368 (2012)
- Dawe GS, "Antipsychotic drugs dose-dependently suppress the spontaneous hyperactivity of the chakragati mouse", Neuroscience, 171, pp.162~172 (2010)
- Renard J, "Long-term consequences of adolescent cannabinoid exposure in adult psychopathology", Front Neurosci, 8, pp.361~ (2014)
- Semple BD, "Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species", Prog Neurobiol, 106-107, pp.1~16 (2013)
- Lian J, "Early antipsychotic exposure affects serotonin and dopamine receptor binding density differently in selected brain loci of male and female juvenile rats", Pharmacol Rep, 68, pp.1028~1035 (2016)
- De Santis M, "Early antipsychotic treatment in juvenile rats elicits long-term alterations to the dopamine neurotransmitter system", Int J Mol Sci, 17, pp.1944~ (2016)
- De Santis M, "Early antipsychotic treatment in childhood", adolescent period has long-term effects on depressive-like, anxiety-like and locomotor behaviours in adult rats, 2016, pp.30, 204~214
- Choi YK, "Effects of repeated risperidone exposure on serotonin receptor subtypes in developing rats", Eur Neuropsychopharmacol, 20, pp.187~194 (2010)
- Natesan S, "Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors : comparing aripiprazole to other antipsychotics in animal models", Neuropsychopharmacology, 31, pp.1854~1863 (2006)
- Reagan-Shaw S, "Dose translation from animal to human studies revisited", FASEB J, 22, pp.659~661 (2008)
- Sestakova N, "Determination of motor activity and anxiety-related behaviour in rodents : methodological aspects and role of nitric oxide", Interdiscip Toxicol, 6, pp.126~135 (2013)
- Moon SJ, "Effect of atomoxetine on hyperactivity in an animal model of attention-deficit", hyperactivity disorder(ADHD), 2014, pp.9, e108918~
- Lalonde R, "The neurobiological basis of spontaneous alternation", Neurosci Biobehav Rev, 26, pp.91~104 (2002)
- Thompson BL, "Prenatal cocaine exposure specifically alters spontaneous alternation behavior", Behav Brain Res, 164, pp.107~116 (2005)
- Xu H, "Chronic haloperidol-induced spatial memory deficits accompany the upregulation of D(1)and D(2)receptors in the caudate putamen of C57BL", 6 mouse, 2012, pp.91, 322~328
- Burda K, "Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats", Pharmacol Rep, 63, pp.898~907 (2011)
- Ratajczak P, "Influence of aripiprazole and olanzapine on behavioral dysfunctions of adolescent rats exposed to stress in perinatal period", Pharmacol Rep, 65, pp.30~43 (2013)
- 이봉주, "Effect of Aripiprazole on Cognitive Function and Hyperprolactinemia in Patients with Schizophrenia Treated with Risperidone", Clinical Psychopharmacology and Neuroscience, 11(2), pp.60~66 (2013), 대한정신약물학회
- Kim SW, "Effectiveness of switching to aripiprazole from atypical antipsychotics in patients with schizophrenia", Clin Neuropharmacol, 32, pp.243~249 (2009)
- Riedel M, "Effect of aripiprazole on cognition in the treatment of patients with schizophrenia", Pharmacopsychiatry, 43, pp.50~57 (2010)
- -raclopride PET study with aripiprazole, "Transl Psychiatry", 2018, 87~
- FDG imaging study with aripiprazole, "Psychopharmacology (Berl)", 2013, 221~229
- Wahlstrom D, "Developmental changes in dopamine neurotransmission in adolescence : behavioral implications and issues in assessment", Brain Cogn, 72, pp.146~159 (2010)
- Moran-Gates T, "Repeated antipsychotic drug exposure in developing rats : dopamine receptor effects", Synapse, 59, pp.92~100 (2006)
- Li Z, "Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain", Eur J Pharmacol, 493, pp.75~83 (2004)
- Spellman T, "Hippocampal-prefrontal input supports spatial encoding in working memory", Nature, 522, pp.309~314 (2015)
- Wilkerson A, "Ventral hippocampal dopamine D1 and D2 systems and spatial working memory in rats", Neuroscience, 89, pp.743~749 (1999)
- Druzin MY, "The effects of local application of D2 selective dopaminergic drugs into the medial prefrontal cortex of rats in a delayed spatial choice task", Behav Brain Res, 109, pp.99~111 (2000)
