title: Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.
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.
authors.affiliation: Department of Neuroscience, Retzius Laboratory, Karolinska Institute, Stockholm, Sweden. anna.mattsson@neuro.ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Mattsson
authors.forename: Eva
authors.initials: E
authors.lastname: Lindqvist
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Ogren
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D020532:Basal Nucleus of Meynert / Q000187:drug effects; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D003714:Denervation / Q000379:methods; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity; D006948:Hyperkinesis / Q000139:chemically induced* / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009699:N-Glycosyl Hydrolases; D009410:Nerve Degeneration / Q000503:physiopathology*; D010622:Phencyclidine / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D014316:Tritium; D016291:Dizocilpine Maleate; D000110:Acetylcholinesterase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D010622:Phencyclidine; D000109:Acetylcholine