Abstract
The α7 nicotinic acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Adult female hooded Lister rats received sub-chronic phencyclidine (PCP) (2 mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days' washout. PCP-treated rats then received PNU-120596 (10 mg/kg; s.c.) or saline and were tested in the attentional set-shifting task. Sub-chronic PCP produced a significant cognitive deficit in the extra-dimensional shift (EDS) phase of the task (p < 0.001, compared with vehicle). PNU-120596 significantly improved performance of PCP-treated rats in the EDS phase of the attentional set-shifting task (p < 0.001). In conclusion, these data demonstrate that PNU-120596 improves cognitive dysfunction in our animal model of cognitive dysfunction in schizophrenia, most likely via modulation of α7 nACh receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Regulation
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Animals
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Attention / drug effects
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Behavior, Animal / drug effects
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Brain / metabolism
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Cognition Disorders / chemically induced
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Cognition Disorders / drug therapy*
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Cognition Disorders / physiopathology
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Discrimination Learning / drug effects
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Disease Models, Animal
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Drug Interactions
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Female
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Half-Life
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Hallucinogens / administration & dosage
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Hallucinogens / toxicity
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Isoxazoles / metabolism
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Isoxazoles / pharmacokinetics
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Isoxazoles / therapeutic use*
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Neurons / metabolism
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Neuroprotective Agents / metabolism
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Neuroprotective Agents / pharmacokinetics
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Neuroprotective Agents / therapeutic use*
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Neurotoxicity Syndromes / drug therapy*
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Neurotoxicity Syndromes / physiopathology
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Nicotinic Agonists / metabolism
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Nicotinic Agonists / pharmacokinetics
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Nicotinic Agonists / therapeutic use*
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Phencyclidine / administration & dosage
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Phencyclidine / toxicity*
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Phenylurea Compounds / metabolism
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Phenylurea Compounds / pharmacokinetics
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Phenylurea Compounds / therapeutic use*
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Rats
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Rats, Inbred Strains
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Receptors, Nicotinic / chemistry*
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Tissue Distribution
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea
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Chrna7 protein, rat
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Hallucinogens
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Isoxazoles
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Neuroprotective Agents
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Nicotinic Agonists
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Phenylurea Compounds
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor
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Phencyclidine