GPCR Regulatory Mechanisms: Effects on Tolerance, Sensitization, and Reinforcement
Laura M. Bohn, Ph.D., Duke University Medical Center

Dr. Laura Bohn discussed research aimed at determining if abrogating µOR desensitization affects the reinforcing and psychomotor properties of morphine, leading to the stimulation of the dopaminergic system. Bohn’s team tested morphine and cocaine in assays of locomotor activity, behavioral sensitization, conditioned place preference, and striatal dopamine release in βarrestin2-knockout (βarr2) mice and their wild-type controls. Bohn concluded that GPCR desensitization by GRK and the βarr2 mechanism play an important role in the actions of drugs of abuse. Specifically, the deletion of GRK-6 appears to selectively affect dopamine or dopamine receptors as opposed to opioid receptors, and the deletion of βarr2 appears to select for opiate effects as opposed to only dopaminergic mediated behaviors.

RGS Protein Function in the Mammalian Brain
Theodore G. Wensel, Ph.D., Baylor College of Medicine

Dr. Theodore Wensel described studies using an RGS9-knockout mice model and a characterization of a retina-specific isoform of RGS9 to examine the molecular pathways regulated by the brain-specific isoform RGS9-2. Wensel explained that his team, along with others, has identified multiple mechanisms for regulating RGS proteins. He concluded that, while the sheer number of such mechanisms is daunting, each of these interactions can be considered a potential site for therapeutic intervention, a discovery that bodes well for addiction research.

Role of Cdk5 in Drug Addiction
James A. Bibb, Ph.D., University of Texas Southwestern Medical Center

Normal as well as aberrant neurotransmission modulates neuronal circuitry through a complex network of signaling pathways that form the basis of synaptic plasticity. Dr. James Bibb presented evidence that implicates Cdk5 in affecting many of these pathways, including the regulation of protein phosphatases. He concluded that Cdk5 may mediate both functional and structural plasticity and may influence learning and memory. Therefore, Cdk5-dependent changes in neuroplasticity may result in an addicted state.