Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia.
Evidence supports a dysregulation of subcortical dopamine (DA) system function as a common etiology of psychosis; however, the factors responsible for this aberrant DA system responsivity have not been delineated. Here, we demonstrate in an animal model of schizophrenia that a pathologically enhanced drive from the ventral hippocampus (vHipp) can result in aberrant dopamine neuron signaling. Adult rats in which development was disrupted by prenatal methylazoxymethanol acetate (MAM) administration display a significantly greater number of spontaneously firing ventral tegmental DA neurons. This appears to be a consequence of excessive hippocampal activity because, in MAM-treated rats, vHipp inactivation completely reversed the elevated DA neuron population activity and also normalized the augmented amphetamine-induced locomotor behavior. These data provide a direct link between hippocampal dysfunction and the hyper-responsivity of the DA system that is believed to underlie the augmented response to amphetamine in animal models and psychosis in schizophrenia patients.
Lodge
Daniel J
DJ
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. Lodge@bns.pitt.edu
Grace
Anthony A
AA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*
D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol; D004298:Dopamine