The Kalivas lab studies neuroplasticity underlying the development of addiction to drugs of abuse, as well as the learning and memory deficits associated with impoverished rearing environments. Research is at the level of protein biochemistry, neural circuitry and behavioral modeling. The current focus for both addiction and isolation rearing is in adaptations in excitatory neurotransmission. In collaboration with electrophysiologists in the department (Drs Lavin, Seamans, Woodward) we are elucidating the fundamental role of extracellular glutamate homeostatis in regulating neurotransmission and neuroplasticity. This has led to preclinical and clinical evaluations of specific proteins as targets in treating addiction, including metabotropic glutamate receptors and the cystine-glutamate exchanger.
Brain circuitry underlying addiction: Long-term cellular changes in the glutamate neurons projecting from the prefrontal cortex to the basal ganglia are critical mediators of addictive behaviors. This includes changes in glutamate homeostasis and G-protein signaling, and involves proteins such as Homer, xCT, AGS3 and mGluRs.