Nicotinic-antipsychotic drug interactions and cognitive function.

Full Abstract

In summary, neuronal nicotinic systems are important for a variety of aspects of cognitive function impacted by antipsychotic drugs. It has been demonstrated that antipsychotic drugs have memory and attentional impairing effects when given to unimpaired subjects. Nicotine can reduce some of these impairments, but antipsychotic drug administration can also attenuate nicotine effects. We have found that nicotinic agonists selective for alpha7 and alpha4beta2 receptor subtypes significantly improve learning and memory. Serotonergic actions of antipsychotic drugs may decrease efficacy of nicotinic co-treatments. When the antipsychotic drug clozapine and nicotine are administered to subjects with cognitive impairments caused by NMDA glutamate receptor blockade or hippocampal dysfunction they can significantly attenuate the attentional and memory impairments. Nicotine has been shown in our studies to reverse the memory impairment caused by acute clozapine-induced memory improvement. Acute risperidone and haloperidol has been shown to attenuate nicotine-induced memory improvement. We have determined the role of hippocampal alpha7 and alpha4beta2 nicotinic receptors in the neural basis of nicotinic antipsychotic interactions. Local acute and chronic hippocampal infusion of either nicotinic alpha7 or alpha4beta2 antagonists cause significant spatial working memory impairment. Chronic hippocampal nicotinic antagonist infusions have served as a model of persistent decreases in nicotinic receptor level seen in schizophrenia and Alzheimer's disease. Clozapine attenuated the memory deficit caused by chronic suppression of hippocampal alpha4beta2 receptors while the amnestic effects of clozapine were potentiated by chronic suppression of hippocampal alpha7 receptors. Nicotinic co-treatment may be a useful adjunct in the treatment of schizophrenia, to attenuate cognitive impairment of schizophrenia. Nicotine as well as selective nicotinic alpha7 and alpha4beta2 receptor agonists significantly improve working memory and attentional function. Nicotine treatment was found to be effective in attenuating the attentional and memory impairments caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of the cognitive impairment of schizophrenia. Studies of the interactions of antipsychotic drugs with nicotinic agents provided quite useful information concerning possible co-treatment of people with schizophrenia with nicotinic therapy. Nicotine was found to significantly attenuate the memory impairments caused by the antipsychotic drugs clozapine and olanzapine. Interestingly, nicotine-induced cognitive improvement was significantly attenuated by the antipsychotic drug clozapine. One of the principal effects of clozapine is to block 5HT2 receptors. Ketanserin a 5HT2 antagonist significantly attenuated nicotine-induced improvements in attention and memory. Thus it appears that antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy of nicotinic co-treatments for cognitive enhancement.

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Author information

Author/s: Levin, Edward D (ED); Rezvani, Amir H (AH);

Affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. edlevin(-atsign-)duke.edu

Grants: MH64494 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Review

Journal: EXS (EXS), published in Switzerland. (Language: eng)

Reference: 2006-; vol 98 (issue ) : pp 185-205

Dates: Created 2006/10/05; Completed 2006/10/31; Revised 2007/11/14;

PMID: 17019889, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals
Antipsychotic Agents - metabolism; pharmacology
Cognition - drug effects; physiology
Drug Interactions

Drug Interactions
Humans
Nicotine - metabolism; pharmacology
Schizophrenia - drug therapy; metabolism

Associated Chemicals: Antipsychotic Agents (0) ; Nicotine (54-11-5)

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