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


OBJECTIVE
In this study, we examined the effect of aripiprazole on cognitive impairment in mice treated with PCP repeatedly.


METHODS
Mice were repeatedly administered PCP at a dose of 10 mg/kg for 14 days, and their cognitive function was assessed using a novel-object recognition task. We investigated the therapeutic effects of aripiprazole (0.01-1.0 mg/kg) and haloperidol (0.3 and 1.0 mg/kg) on cognitive impairment in mice treated with PCP repeatedly.


RESULTS
Single (1.0 mg/kg) and repeated (0.03 and 0.1 mg/kg, for 7 days) 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 1.0 mg/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.
Nagai
Taku
T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Murai
Rina
R
Matsui
Kanae
K
Kamei
Hiroyuki
H
Noda
Yukihiro
Y
Furukawa
Hiroshi
H
Nabeshima
Toshitaka
T
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D021641:Recognition, Psychology / Q000187:drug effects*
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D015363:Quinolones; D017447:Receptors, Dopamine D1; D044282:Receptor, Serotonin, 5-HT1A; D000068180:Aripiprazole; D010622:Phencyclidine; D006220:Haloperidol