Amygdala Hyperactivity in MAM Model of Schizophrenia is Normalized by Peripubertal Diazepam Administration.

Abstract

In addition to prefrontal cortex (PFC) and hippocampus, amygdala may have a role in the pathophysiology of schizophrenia, given its pivotal role in emotion and extensive connectivity with the PFC and hippocampus. Moreover, abnormal activities of amygdala may be related to the anxiety observed in schizophrenia patients and at-risk adolescents. These at-risk subjects demonstrated heightened levels of anxiety, which are correlated with the onset of psychosis later in life. Similarly, rats that received methyl azoxymethanol acetate (MAM) gestationally exhibited higher levels of anxiety peripubertally. In the current study, the heightened anxiety was also observed in adult MAM animals, as well as higher firing rates of BLA neurons in both peripubertal and adult MAM rats. In addition, the power of BLA theta oscillations of adult MAM rats showed a larger increase in response to conditioned stimuli (CS). We showed previously that administration of the antianxiety drug diazepam during the peripubertal period prevents the hyperdopaminergic state in adult MAM rats. In this study, we found that peripubertal diazepam treatment reduced heightened anxiety, decreased BLA neuron firing rates and attenuated the CS-induced increase in BLA theta power in adult MAM rats, supporting a persistent normalization by this treatment. This study provides a link between BLA hyperactivity and anxiety in schizophrenia model rats and that circumvention of stress may prevent the emergence of pathology in the adult.