title: Nicotinic cholinergic normalization of amphetamine-induced loss of auditory gating in freely moving rats.
abstract: The impairment in normal sensory processing which is usually observed in schizophrenics has been demonstrated using a paired-stimulus paradigm. Normal individuals show a diminished midlatency evoked potential response to the second of a pair of clicks given at a 0.5-s interval. This phenomenon is termed auditory "gating". Schizophrenics routinely fail to suppress their response to the second click in this paradigm; thus, they do not gate. Heavy tobacco use is common among schizophrenics and it has recently been shown that nicotine causes a transient normalization of auditory gating in these individuals. Our laboratory has been utilizing animal models to investigate the sensory deficit observed in schizophrenia. In the present study, rats were administered amphetamine to produce a schizophrenia-like loss of auditory gating. They were then given nicotine, which resulted in a dose-dependent normalization of the amphetamine-induced loss of gating. This effect was blocked by concurrent central administration of d-tubocurarine. Neither nicotine nor d-tubocurarine had any effect on auditory gating when administered alone. These data are in agreement with the human studies showing normalization of auditory gating with nicotine administration and suggest a possible role for the nicotinic cholinergic receptor in the modulation of auditory gating in the rat model.
authors.affiliation: Department of Psychiatry, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Stevens
authors.forename: J
authors.initials: J
authors.lastname: Meltzer
authors.forename: G M
authors.initials: GM
authors.lastname: Rose
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D017950:Ganglia, Sensory / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D013997:Time Factors; D014403:Tubocurarine / Q000494:pharmacology
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine; D000661:Amphetamine; D014403:Tubocurarine