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Effects of nicotine on schizophrenia-like cognitive deficits

Institution: University of California, San Diego
Investigator(s): Nurith Amitai, B.S.
Award Cycle: 2006 (Cycle 15) Grant #: 15DT-0048 Award: $58,298
Subject Area: Nicotine Dependence
Award Type: Dissertation Awards
Abstracts

Initial Award Abstract
Rates of tobacco smoking are increasedelevated in various psychiatric populations. This phenomenon is most striking in schizophrenia patients, almost 90% of whom smoke. This is drastically higher than the general smoking rate of about 25-30%, and is compounded by the fact that most of these patients are very heavy smokers. As a result, schizophrenia patients are disproportionately affected by tobacco-related diseases, which exact a heavy toll on both society and the individual through medical costs, personal suffering, and early mortality.

The high smoking rates among schizophrenia patients may be due to patients using tobacco to alleviate some of their schizophrenia symptoms. While current antipsychotic treatments are quite successful in controlling the better known schizophrenia symptoms, such as hallucinations and delusions (the so-called positive symptoms), they have no or only very limited effects on other symptom clusters. One such symptom cluster is the presence of cognitive deficits, such as difficulty focusing attention, impaired memory and learning, and cognitive inflexibility. These deficits cause severe difficulties for schizophrenia sufferers and can lead to chronic disability. Nicotine is the key psychoactive component driving tobacco use. Various studies have reported that nicotine can improve cognition under some circumstances, especially in individuals with cognitive problems. Indeed, the pro-cognitive effects of nicotine may be a significant factor driving smoking. In particular, schizophrenia patients may smoke tobacco to reduce their cognitive symptoms.

Pharmacological manipulations that mimic schizophrenia symptoms allow the development of experimental models that permit controlled studies of various aspects of the disorder, and how nicotine administration may affect these aspects. One such compound is phencyclidine (PCP), which produces a psychosis-like state that closely resembles schizophrenia and responds similarly to antipsychotic treatment. This raises the possibility that PCP may affect some of the same underlying neural systems as those mediating schizophrenia.

Accordingly, the proposed research will use PCP to induce schizophrenia-like cognitive deficits, so as to explore the effects of nicotine on these deficits. In this way, the proposed studies will examine the hypothesis that nicotine alleviates cognitive symptoms of schizophrenia, supporting the hypothesis that increased tobacco smoking in schizophrenia is due to attempts to medicate these symptoms. The effects of nicotine on PCP-induced disruption will be studied in a range of cognitive tasks, including tests assessing attention, working memory, and cognitive flexibility, as well as reward function, using well established behavioral tests for these functions. Further, Tthe proposed studies will also investigate how PCP affects levels of neurotransmitters in the brain, and how nicotine exposure changes these effects. Focusing on brain areas crucially involved in cognition, these observations will shed light on how, on a neuropharmacological
Publications

Cognitive-disruptive effects of the psychotomimetic Phencyclidine and attenuation by atypical antipsychotic medications in rats.
Periodical: Psychopharmacology Index Medicus:
Authors: Nurith, Amitai ABS
Yr: 2007 Vol: 4 Nbr: Abs: Pg: 521-537

Clozapine paetially attenuates cognitive deficits inducedc by the psychotomimetic Phencyclidine.
Periodical: Behavioral Pharmacology Index Medicus:
Authors: Amitai, N., Semenova, S., Markou, A ABS
Yr: 2007 Vol: 18 Nbr: S68 Abs: Pg:

Chronic nicotine improves cognitive performance in a test of attention, but does not attenuate cognitive disruption induced by repeated phecyclidine administration
Periodical: Psychopharmacology Index Medicus:
Authors: Amitai, N. ART
Yr: 2008 Vol: Nbr: Abs: Pg:

Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medicationsin rats
Periodical: Psychopharmacology Index Medicus:
Authors: Amitai, N. ART
Yr: 2007 Vol: 193 Nbr: Abs: Pg: 521-37