title: Hippocampal deep brain stimulation reverses physiological and behavioural deficits in a rodent model of schizophrenia.
abstract: Subcortical dopamine system dysregulation has been suggested to underlie the positive symptoms of schizophrenia. Recent preclinical investigations and human imaging studies have proposed that the augmented dopamine system function observed in schizophrenia patients may be secondary to aberrant hippocampal activity. Thus, we posit that the hippocampus represents a novel therapeutic target for the treatment of schizophrenia. Here we provide evidence of the effectiveness of a unique approach aimed at decreasing hippocampal function in a rodent model of schizophrenia. Specifically, in a rodent model of schizophrenia, we demonstrate that ventral hippocampal (vHipp) deep brain stimulation (DBS) can normalize aberrant dopamine neuron activity and behaviours associated with positive symptoms. In addition, we provide evidence that this approach may also be effective in restoring deficits in cognitive function, often left unaltered by conventional antipsychotic medications. Therefore, we have provided initial preclinical evidence demonstrating the feasibility of hippocampal DBS as a potential novel approach for the treatment of schizophrenia.
authors.affiliation: Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perez
authors.forename: Amiksha
authors.initials: A
authors.lastname: Shah
authors.forename: Amber
authors.initials: A
authors.lastname: Asher
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006948:Hyperkinesis / Q000139:chemically induced; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000628:therapy*; D008746:Methylazoxymethanol Acetate / Q000633:toxicity; D009498:Neurotoxins / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000150:complications* / Q000209:etiology / Q000628:therapy; D017557:Ventral Tegmental Area / Q000473:pathology
chemical_list: D009498:Neurotoxins; D008746:Methylazoxymethanol Acetate; D000661:Amphetamine