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Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

Anna Mattsson·Eva Lindqvist·Sven Ove Ogren·Lars Olson
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Abstract

Altered cholinergic function is considered as a potential contributing factor in the pathogenesis of schizophrenia. We hypothesize that cortical cholinergic denervation may result in changes in glutamatergic activity. Therefore, we lesioned the cholinergic corticopetal projections by local infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of rats. Possible effects of this lesion on glutamatergic systems were examined by phencyclidine-induced locomotor activity, and also by N-methyl-D-aspartate receptor binding. We find that cholinergic lesioning of neocortex leads to enhanced sensitivity to phencyclidine in the form of a dramatic increase in horizontal activity. Further, N-methyl-D-aspartate receptor binding is unaffected in denervated rats. These results suggest that aberrations in cholinergic function might lead to glutamatergic dysfunctions, which might be of relevance for the pathophysiology for schizophrenia.

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AcetylcholineAcetylcholinesteraseAnalysis of VarianceAnimalsAntibodies, MonoclonalBasal Nucleus of MeynertBehavior, AnimalCerebral CortexDenervationDizocilpine MaleateDose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsHyperkinesisImmunohistochemistryImmunotoxinsMaleMotor ActivityN-Glycosyl HydrolasesNerve DegenerationPhencyclidineProtein BindingRadioligand AssayRatsRats, Sprague-DawleyRibosome Inactivating Proteins, Type 1SaporinsTritiumComparative StudyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Anna Mattsson, Eva Lindqvist, Sven Ove Ogren, Lars Olson. 2005-11-07. Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.. https://doi.org/10.1097/01.wnr.0000185018.29316.87

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