title: Vagal nerve stimulation reverses aberrant dopamine system function in the methylazoxymethanol acetate rodent model of schizophrenia.
abstract: Vagal nerve stimulation (VNS) is an alternative therapy for epilepsy and treatment refractory depression. Here we examine VNS as a potential therapy for the treatment of schizophrenia in the methylozoxymethanol acetate (MAM) rodent model of the disease. We have previously demonstrated that hyperactivity within ventral regions of the hippocampus (vHipp) drives the dopamine system dysregulation in this model. Moreover, by targeting the vHipp directly, we can reverse aberrant dopamine system function and associated behaviors in the MAM model. Although the central effects of VNS have not been completely delineated, positron emission topographic measurements of cerebral blood flow in humans have consistently reported that VNS stimulation induces bilateral decreases in hippocampal activity. Based on our previous observations, we performed in vivo extracellular electrophysiological recordings in MAM- and saline-treated rats to evaluate the effect of chronic (2 week) VNS treatment on the activity of putative vHipp pyramidal neurons, as well as downstream dopamine neuron activity in the ventral tegmental area. Here we demonstrate that chronic VNS was able to reverse both vHipp hyperactivity and aberrant mesolimbic dopamine neuron function in the MAM model of schizophrenia. Additionally, VNS reversed a behavioral correlate of the positive symptoms of schizophrenia. Because current therapies for schizophrenia are far from adequate, with a large number of patients discontinuing treatment due to low efficacy or intolerable side effects, it is important to explore alternative nonpharmacological treatments. These data provide the first preclinical evidence that VNS may be a possible alternative therapeutic approach for the treatment of schizophrenia.
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perez
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and.
authors.forename: Flavia R
authors.initials: FR
authors.lastname: Carreno
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas 78229.
authors.forename: Alan
authors.initials: A
authors.lastname: Frazer
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, and LodgeD@uthscsa.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008746:Methylazoxymethanol Acetate; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*
chemical_list: D009498:Neurotoxins; D008746:Methylazoxymethanol Acetate
keywords: dopamine; hippocampus; schizophrenia; vagal nerve stimulation