TY - JOUR T1 - Aberrant Hippocampal Activity Underlies the Dopamine Dysregulation in an Animal Model of Schizophrenia JF - The Journal of Neuroscience JO - J. Neurosci. SP - 11424 LP - 11430 DO - 10.1523/JNEUROSCI.2847-07.2007 VL - 27 IS - 42 AU - Daniel J. Lodge AU - Anthony A. Grace Y1 - 2007/10/17 UR - http://www.jneurosci.org/content/27/42/11424.abstract N2 - 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. ER -