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The Journal of Neuroscience, October 17, 2007, 27(42):11424-11430; doi:10.1523/JNEUROSCI.2847-07.2007

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Neurobiology of Disease
Aberrant Hippocampal Activity Underlies the Dopamine Dysregulation in an Animal Model of Schizophrenia

Daniel J. Lodge and Anthony A. Grace

Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Correspondence should be addressed to Daniel J. Lodge, Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260. Email: Lodge{at}bns.pitt.edu

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.

Key words: hippocampus; schizophrenia; MAM; dopamine; psychosis; animal model

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Received June 22, 2007; revised Sept. 6, 2007; accepted Sept. 6, 2007.

Correspondence should be addressed to Daniel J. Lodge, Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260. Email: Lodge{at}bns.pitt.edu

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