title: Cholinergic gating of hippocampal auditory evoked potentials in freely moving rats.
abstract: As perturbations in auditory filtering appear to be a candidate trait marker of schizophrenia, there has been considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in sensory gating. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine, the muscarinic M1 antagonist biperiden and the cholinesterase inhibitor donepezil (also in combination with scopolamine and biperiden) on auditory evoked potentials (AEPs) and sensory gating. In the saline condition, only the N50 peak displayed sensory gating. Scopolamine and biperiden both disrupted sensory gating by increasing N50 amplitude for the S2 click. Donepezil was able to fully reverse the effects of biperiden on N50 sensory gating, but had residual effects when combined with scopolamine; i.e., it enhanced sensory gating by increasing N50 amplitude of the S1 stimulus. Donepezil by itself improved sensory gating by enhancing N50 amplitude of S1, and reducing N50 amplitude of the S2 click. In conclusion, due to its relatively more selective effects biperiden is to be preferred over scopolamine as a means for pharmacologically inducing cholinergic impairments in auditory processing in healthy rats. Changes in auditory processing and sensory gating induced by cholinergic drugs may serve as a translational model for aging instead of schizophrenia.
authors.affiliation: Faculty of Psychology and Neuroscience, Department of Neuropsychology and Psychopharmacology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. inge.klinkenberg@maastrichtuniversity.nl
authors.forename: Inge
authors.initials: I
authors.lastname: Klinkenberg
authors.forename: Anke
authors.initials: A
authors.lastname: Sambeth
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001712:Biperiden / Q000031:analogs & derivatives / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D000077265:Donepezil; D004569:Electroencephalography / Q000187:drug effects; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007189:Indans / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology; D055139:Sensory Gating / Q000187:drug effects
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D010880:Piperidines; D043643:Receptor, Muscarinic M1; C036432:biperiden lactate; D001712:Biperiden; D000077265:Donepezil; D012601:Scopolamine