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Br J Pharmacol. 2014 Apr;171(7):1758-71. doi: 10.1111/bph.12578.

Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia.

Author information

1
Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.

Abstract

BACKGROUND AND PURPOSE:

The prevalence of smoking in schizophrenia patients is exceptionally high; it is not known why but many researchers suggest that smoking constitutes a form of self-medication. Among the symptoms of schizophrenia that may be improved by nicotine are cognitive deficits. Hence, we studied the effects of long-term nicotine administration on cognition in a genetic animal model of schizophrenia susceptibility, G72-transgenic (G72Tg) mice.

EXPERIMENTAL APPROACH:

The effect of long-term nicotine or saline, administered by osmotic minipumps, on different cognitive domains was assessed in G72Tg mice and controls using a battery of behavioural tests. To investigate the mechanism underlying phenotypic differences, quantitative autoradiographic mapping of nACh receptor subtypes was performed in forebrain structures to explore effects of chronic nicotine exposure on nACh receptor density in wild-type (WT) and G72Tg mice.

KEY RESULTS:

Genotype significantly affected the cognitive effects of chronic nicotine administration. Whereas chronic nicotine disrupted cognitive performance in WT mice, it was effective at restoring impaired prepulse inhibition, working memory and social recognition in G72Tg mice. However, long-term spatial learning was further impaired by nicotine in transgenic animals. In contrast, associative learning was protected by G72-expression against the adverse nicotine effects seen in WT animals. G72-expression did not decisively influence nicotine-induced up-regulation of the α4β2*subtype, whereas α7nACh receptor density was differentially altered by genotype or by a genotype·treatment interaction in specific brain areas, most notably hippocampal subregions.

CONCLUSIONS AND IMPLICATIONS:

Our data support the hypothesis that nicotine self-medication of schizophrenics improves cognitive symptoms, possibly by facilitating nicotine-induced α7nACh receptor activation in the hippocampus.

KEYWORDS:

G72 mouse model; G72/G30 gene locus; chronic nicotine; cognition; nicotinic acetylcholine receptor; receptor autoradiography; schizophrenia; self-medication; short-term memory; susceptibility gene

PMID:
24417347
PMCID:
PMC3966754
DOI:
10.1111/bph.12578
[Indexed for MEDLINE]
Free PMC Article

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