Differential expression of CRP40 protein and its affects on dopamine-dependent behaviours and dopamine-activity

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Catecholamines are neurotransmitters found in both the peripheral and central nervous system (CNS). CNS catecholamines consist of dopamine (DA) and its two hydroxylated products, norepinephrine, and epinephrenine. DA constitutes approximately 80% of catecholamines in the brain and, via its effects on specific receptors, is an important neurochemical mediator in behaviours. Likewise, aberrations in DA activity have been implicated in abnormal behaviour. Importantly, DA's effect in these domains is activity dependent and tightly coupled to extracellular DA levels in the synapse. However, relatively little is known about the molecular mechanisms that regulate levels of DA. The proposed research program seeks to investigate the role of a 40kDa catecholamine regulating protein (CRP40) in governing DA levels and, in turn, DA-dependent behaviour. This line of investigation is interesting given that my lab has shown that CRP40 is a multifunctional protein with catecholamine binding functions. Moreover, CRP40 may act as a scavenging molecule in the presence of excess DA activity. Arguably, these processes each represent potential components in the overall regulation of DA and bolster the suggestion that CRP40 has a fundamental impact on CNS DA levels and, consequently, DA-dependent behaviour. What is missing, however, are studies aimed at experimentally testing the impact of CRP40 manipulations on dopaminergic molecules causing alterations on DA concentrations, and DA-dependent behavior in order to elucidate these putative underlying relationships. The proposed approach in this research program will involve rat brain region specific knock-down of CRP40 mRNA in order to examine how the time-course of CRP40 knockdown and recovery is coupled to changes in several DA-dependent behaviours. Based on the hypothesis that CRP40 regulates DA activity, we predict that dysfunction and recovery of DA-dependent behaviours will follow the time-course of CRP40 protein recovery.