Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors
- 832 Downloads
Cognitive deficits, including memory impairment, are regarded as a core feature of schizophrenia. Aripiprazole, an atypical antipsychotic drug, has been shown to improve disruption of prepulse inhibition and social interaction in an animal model of schizophrenia induced by phencyclidine (PCP); however, the effects of aripiprazole on recognition memory remain to be investigated.
In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly.
Materials and methods
Mice were repeatedly administered PCP at a dose of 10mg/kg for 14days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01–1.0mg/kg) and haloperidol (0.3 and 1.0mg/kg) on cognitive impairment in mice treated with PCP repeatedly.
Single (1.0mg/kg) and repeated (0.03 and 0.1mg/kg, for 7days) treatment with aripiprazole ameliorated PCP-induced impairment of recognition memory, although single treatment significantly decreased the total exploration time during the training session. In contrast, both single and repeated treatment with haloperidol (0.3 and 1.0mg/kg) failed to attenuate PCP-induced cognitive impairment. The ameliorating effect of aripiprazole on recognition memory in PCP-treated mice was blocked by co-treatment with a dopamine D1 receptor antagonist, SCH23390, and a serotonin 5-HT1A receptor antagonist, WAY100635; however, co-treatment with a D2 receptor antagonist raclopride had no effect on the ameliorating effect of aripiprazole.
These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.
KeywordsAripiprazole Dopamine D1 receptor Memory Phencyclidine Serotonin 5-HT1A receptor
This work was supported, in part, as Research on Regulatory Science of Pharmaceuticals and Medical Devices, and Research on Risk of Chemical Substances, Health and Labour Sciences Research Grants from the Ministry of Health, Labor and Welfare, Japan, Academic Frontier Project for Private Universities (2007–2011) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and from Uehara Memorial Foundation, International Research Project supported by The Meijo Asian Research Center (MARC). We are grateful to Otsuka Pharmaceutical Co. for providing the aripiprazole.
- Enomoto T, Noda Y, Mouri A, Shin EJ, Wang D, Murai R, Hotta K, Furukawa H, Nitta A, Kim HC, Nabeshima T (2005) Long-lasting impairment of associative learning is correlated with a dysfunction of N-methyl-d-aspartate-extracellular signaling-regulated kinase signaling in mice after withdrawal from repeated administration of phencyclidine. Mol Pharmacol 68:1765–1774PubMedGoogle Scholar
- Hagiwara H, Fujita Y, Ishima T, Kunitachi S, Shirayama Y, Iyo M, Hashimoto K (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antipsychotic drug perospirone: role of serotonin 5-HT1A receptors. Eur Neuropsychopharmacol 18:448–454PubMedCrossRefGoogle Scholar
- Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O’Laughlin IA, Meltzer HY (2001) 5-HT2A and D2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76:1521–1531PubMedCrossRefGoogle Scholar
- Ito M, Nagai T, Mizoguchi H, Fukakusa A, Nakanishi Y, Kamei H, Nabeshima T, Takuma K, Yamada K (2007a) Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system. J Neurochem 101:1392–1399PubMedCrossRefGoogle Scholar
- Ito Y, Takuma K, Mizoguchi H, Nagai T, Yamada K (2007b) A novel azaindolizinone derivative ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2. J Pharmacol Exp Ther 320:819–827PubMedCrossRefGoogle Scholar
- Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE (1993) Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenia. Neuropsychopharmacol 8:315–336Google Scholar
- Kamei H, Nagai T, Nakano H, Togan Y, Takayanagi M, Takahashi K, Kobayashi K, Yoshida S, Maeda K, Takuma K, Nabeshima T, Yamada K (2006) Repeated methamphetamine treatment impairs recognition memory through a failure of novelty-induced ERK1/2 activation in the prefrontal cortex of mice. Biol Psychiatry 59:75–84PubMedCrossRefGoogle Scholar
- Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA, CATIE InvestigatorsNeurocognitive Working Group (2007) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:633–647PubMedCrossRefGoogle Scholar
- Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, Morita S (1995) 7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther 274:329–336PubMedGoogle Scholar
- Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, Lopez JF, Watson SJ (2004) Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry 55:225–233PubMedCrossRefGoogle Scholar
- McQuade RD, Burris KD, Jordan S, Tottori K, Kurahashi N, Kikuchi T (2002) Aripiprazole: a dopamine–serotonin system stabilizer. Int Neuropsychopharmacol 5(Suppl. 1):S176Google Scholar
- Meltzer HY (1999) The role of serotonin in antipsychotic drug action. Neuropsychopharmacol 21:106S–115SGoogle Scholar
- Mouri A, Noda Y, Noda A, Nakamura T, Tokura T, Yura Y, Nitta A, Furukawa H, Nabeshima T (2007b) Involvement of a dysfunctional dopamine-D1/N-methyl-d-aspartate-NR1 and Ca2+/calmodulin-dependent protein kinase II pathway in the impairment of latent learning in a model of schizophrenia induced by phencyclidine. Mol Pharmacol 71:1598–1609PubMedCrossRefGoogle Scholar
- Murai R, Noda Y, Matsui K, Kamei H, Mouri A, Matsuba K, Nitta A, Furukawa H, Nabeshima T (2007) Hypofunctional glutamatergic neurotransmission in the prefrontal cortex is involved in the emotional deficit induced by repeated treatment with phencyclidine in mice: implications for abnormalities of glutamate release and NMDA-CaMKII signaling. Behav Brain Res 180:152–160PubMedCrossRefGoogle Scholar
- Nagai T, Takuma K, Kamei H, Ito Y, Nakamichi N, Ibi D, Nakanishi Y, Murai M, Mizoguchi H, Nabeshima T, Yamada K (2007) Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex. Learn Mem 14:117–125PubMedCrossRefGoogle Scholar
- Rainey Jr JM, Crowder MK (1975) Prolonged psychosis attributed to phencyclidine: report of three cases. Am J Psychiatry 132:1076–1078Google Scholar
- Shimokawa Y, Akiyama H, Kashiyama E, Koga T, Miyamoto G (2005) High performance liquid chromatographic methods for the determination of aripiprazole with ultraviolet detection in rat plasma and brain: application to the pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 821:8–14PubMedCrossRefGoogle Scholar
- Stark AD, Jordan S, Allers KA, Bertekap RL, Chen R, Mistry Kannan T, Molski TF, Yocca FD, Sharp T, Kikuchi T, Burris KD (2007) Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies. Psychopharmacology 190:373–382PubMedCrossRefGoogle Scholar