Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses subcronic PCP-induced deficits in the novel object recognition task in rats
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Trine Damgaard Nielsen, Dorrit Bjerg Larsen, Suzanne Lisbet Hansen, Ben Grayson, Jo C. Neill, Niels Plath
Cognitive deficits are a major clinical unmet need in schizophrenia. The psychotomimetic drug phencyclicline (PCP) is widely applied in rodents to mimic symptoms of schizophrenia, including cognitive deficits. Precious studies have shown that sub-chronic PCP induces an enduring episodic memory deficit in female Lister hooded rats in teh novel object recognition (NOR) task. Here we show that positive modulation of AMPA receptor (AMPAR) mediated glutamate transmission alleviates cognitive deficits induced by sub-chronic PCP treatment. Female Lister hooded rats were treated sub-cronically with either vehicle (0.9% saline) or PCP (2mg/kg two doses per day for 7 days), followed by a 7 days washout period. 30 min prior to the acquisition trial of the NOR task animals were dosed with either vehicle, CX546 (10, 40, or 80 mg/kg) or CX516 (0.5, 2.5, 10, 40, or 80 mg/kg). Our results show that sub-cbronic PCP treatment induced a significant decrease in the discrimination index (DI) and both ampakines CX546 and CX516 were able to reverse this diruption of object memory in rats in the novel object recognition task. These data suggest that positive AMPAR modulation may represent a mechanism for treatment of cognitive deficits in schizophrenia. (C) 2009 Elsevier B.V. All rights reserved.
|Tidsskrift||Behavioural Brain Research|
|Status||Udgivet - 11 feb. 2010|
- Det Farmaceutiske Fakultet - Schizophrenia, Cognition, Phencyclidine, Ampakines, Novel object recognition, Rats