Original Investigation

Psychopharmacology

, Volume 202, Issue 1, pp 315-328

First online:

Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors

  • Taku NagaiAffiliated withDepartment of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine
  • , Rina MuraiAffiliated withDepartment of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University
  • , Kanae MatsuiAffiliated withDepartment of Health-Care Pharmacy, Graduate School of Pharmaceutical Sciences, Meijo University
  • , Hiroyuki KameiAffiliated withDepartment of Health-Care Pharmacy, Graduate School of Pharmaceutical Sciences, Meijo University
  • , Yukihiro NodaAffiliated withDivision of Clinical Science in Clinical Pharmacy Practice, Graduate School of Pharmaceutical Sciences, Meijo University
  • , Hiroshi FurukawaAffiliated withDepartment of Medical Chemistry, Graduate School of Pharmaceutical Sciences, Meijo University
  • , Toshitaka NabeshimaAffiliated withDepartment of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of MedicineDepartment of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University Email author 

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Abstract

Rationale

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.

Objectives

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.

Results

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.

Conclusions

These results suggest that the ameliorative effect of aripiprazole on PCP-induced memory impairment is associated with dopamine D1 and serotonin 5-HT1A receptors.

Keywords

Aripiprazole Dopamine D1 receptor Memory Phencyclidine Serotonin 5-HT1A receptor