Premium
Chronic nicotine improves short‐term memory selectively in a G 72 mouse model of schizophrenia
Author(s) -
Hambsch B,
Keyworth H,
Lind J,
Otte D M,
Racz I,
Kitchen I,
Bailey A,
Zimmer A
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12578
Subject(s) - nicotine , prepulse inhibition , schizophrenia (object oriented programming) , hippocampal formation , morris water navigation task , forebrain , cognition , medicine , psychology , endocrinology , pharmacology , neuroscience , psychiatry , central nervous system
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, G 72‐transgenic ( G72T g) mice. Experimental Approach The effect of long‐term nicotine or saline, administered by osmotic minipumps, on different cognitive domains was assessed in G72T g mice and controls using a battery of behavioural tests. To investigate the mechanism underlying phenotypic differences, quantitative autoradiographic mapping of n ACh receptor subtypes was performed in forebrain structures to explore effects of chronic nicotine exposure on n ACh receptor density in wild‐type ( WT ) and G72T g 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 G72T g mice. However, long‐term spatial learning was further impaired by nicotine in transgenic animals. In contrast, associative learning was protected by G 72‐expression against the adverse nicotine effects seen in WT animals. G 72‐expression did not decisively influence nicotine‐induced up‐regulation of the α4β2*subtype, whereas α7n ACh 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 α7n ACh receptor activation in the hippocampus.