This is a proposal for continuation of a Research Scientist Award directed toward mental health issues at the interface between the basic and clinical sciences. I plan to continue to explore the mechanisms involved in the adaptive aspects of the several biogenic amine systems, because I have previously provided evidence that these adaptations serve a restitutive or buffering function in the brain. In the case of the dopaminergic system I have proposed that this restitutive system serves to prevent psychotic destabilization in the face of chronic unavoidable stress. In the past period I have developed a model, in rats, of the function of this restitutive system. This model involves training rats to perform the conditioned avoidance response (CAR) which is inhibited by all neuroleptic drugs. With my collaborators, I have produced pilot evidence that chronic inescapable stress also leads to inhibition of the CAR, showing that the brain is capable of making a neuroleptic-like response to persistant adversity. In other studies we are investigating the mechanism of this and other aminergic response s at the genomic and synaptic levels, as well as the effect of prenatal factors on the development of this adaptive capacity.
