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Neurotox Res. 2007 Dec;12(4):233-46.

Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia.

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  • 1Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA.


Schizophrenia is a complex neuropsychiatric disorder with devastating consequences. It is characterized by thought fragmentation, hallucination and delusion, collectively referred to as positive symptoms. In addition, mood changes or affective disorders, referred to as negative symptoms, as well as cognitive impairments can be manifested in these patients. Arguably, modeling such a disorder in its entirety in animals might not be feasible. Despite this limitation, various models with significant construct, predictive and some face validity have been developed. One such model, based on hypoglutamatergic hypothesis of schizophrenia, makes use of administering NMDA receptor antagonists and evaluating behavioral paradigms such as sensorimotor gating. Because of very high incidence of smoking among schizophrenic patients, it has been postulated that some of these patients may actually be self medicating with tobacco's nicotine. Research on nicotinic-glutamatergic interactions using various animal models has yielded conflicting results. In this review, some of these models and possible confounding factors are discussed. Overall, a therapeutic potential for nicotinic agonists in schizophrenia can be suggested. Moreover, it is evident that various experimental paradigms or models of schizophrenia symptoms need to be combined to provide a wider spectrum of the behavioral phenotype, as each model has its inherent limitations.

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