My laboratory is interested in the role of the central synaptic and intrinsic neuronal properties in cocaine addiction. Our recent work investigates the role of the protein kinase M zeta (PKM) and the Ih current in the development of cocaine sensitization, a progressive and lasting enhancement in the motor stimulant effect induced by a subsequent drug challenge. Experiments include the use of animal models, western blots, systemic and intracranial administration of agonists and antagonists together with in vivo behavioral recordings. Whole cell patch clamp neurophysiologic recording techniques in in vitro brain slices are also employed to understand the basic biophysical mechanisms of cocaine addiction. The completion of these investigations will provide important information of whether a dysfunction of these modulatory properties are important factosr in the development of cocaine addiction and could suggest possible avenues for therapeutic pharmacological interventions.