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Psychopharmacology (Berl). 2009 Nov;206(4):631-40. doi: 10.1007/s00213-009-1540-5. Epub 2009 Apr 24.

Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia--sub-chronic and early postnatal PCP treatment in attentional set-shifting.

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  • 1Department of In Vivo Neurobiology, H. Lundbeck A/S, Ottiliavej 9, Valby, Denmark. bbs@lundbeck.com

Abstract

RATIONALE:

Therapies treating cognitive impairments in schizophrenia especially deficits in executive functioning are not available at present.

OBJECTIVE:

The current study evaluated the effect of ampakine CX516 in reversing deficits in executive functioning as represented in two animal models of schizophrenia and assessed by a rodent analog of the intradimensional-extradimensional (ID-ED) attentional set-shifting task. The second generation antipsychotic, sertindole, provided further validation of the schizophrenia-like disease models.

METHODS:

Animals were subjected to (a) sub-chronic or (b) early postnatal phencyclidine (PCP) treatment regimes: (a) Administration of either saline or PCP (5 mg/kg, intraperitonally b.i.d. for 7 days) followed by a 7-day washout period and testing on day 8. (b) On postnatal days (PNDs) 7, 9, and 11, rats were subjected to administration of either saline or PCP (20 mg/kg, subcutaneously (s.c.)) and tested on PNDs 56-95, after reaching adulthood. The single test session required rats to dig for food rewards in a series of discriminations following acute administration of either vehicle, or CX516 (5-40 mg/kg, s.c.), or sertindole (1.25 mg/kg, perorally).

RESULTS:

The specific extradimensional deficits produced by sub-chronic or early postnatal PCP treatment were significantly attenuated by sertindole and dose-dependently by CX516.

CONCLUSION:

Findings here further establish PCP treatment as model of executive functioning deficits related to schizophrenia and provide evidence that direct glutamatergic interventions could improve these, when assessed in the ID-ED attentional set-shifting task.

PMID:
19390843
[PubMed - indexed for MEDLINE]
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