Neonatal Amygdala Lesions and Stress Responsivity in Rats : Relevance to schizophrenia

Abstract

"Stress responsiveness in an animal model with relevance to schizophrenia”

Rats bearing lesions of the amygdala made on postnatal day 7 (D7 AMX) model aspects of neurodevelopmental psychopathologies, such as schizophrenia. Adult D7 AMX rats display impaired pre-pulse inhibition, impaired behavioral responses to stress, impaired social behavior, and increased sensitivity to phencyclidine. Some of these symptoms become manifest after puberty, as is the case in schizophrenic patients, and are not observed in rats in which the amygdalae are lesioned on postnatal day 21 (D21 AMX), suggesting altered development of brain structures that are innervated by the amygdala under normal conditions. Alternately, schizophrenic patients have an adaptational deficit. Not only do life events appear to increase the risk of psychotic relapse and the number of daily life stressors relate to the number of schizophrenic symptoms, but schizophrenic patients also have a diminished Hypothalamic-pituitary-adrenal (HPA) response to a variety of stressful stimuli.

Therefore, in this thesis, stress responsiveness was investigated in the D7 AMX model. This included HPA and sympathetic-adrenomedullary (SAM) axis responsivity to novelty and foot shock stimuli, glucocorticoid feedback and pituitary-adrenal sensitivity to CRH, circadian corticosterone rhythmicity, α 1- and α 2-adrenoceptor density in several brain regions of interest and the effect of neuroleptic treatment on HPA axis responsivity. The results show that dysfunction of the amygdala in early life can result in disturbed development and function of the HPA axis, one of the organism's major adaptational systems, and underline the relevance of the D7 AMX model for aspects of neurodevelopmental psychopathological disorders such as schizophrenia. In view of the similarities in symptoms between the D7 AMX rat model and schizophrenia, the results support the D7 AMX model as an interesting model for the testing of pharmacological agents which amongst others might benefit stress responsivity, and call for further research on the role of the amygdala complex and the HPA axis schziophrenia.