Kalivas Laboratory

Our lab conducts experiments intended to reveal the neurobiological underpinnings of substance use disorders and anxiety disorders such as PTSD. In doing so, we endeavor to identify molecular targets and provide biological rationales for designing pharmacotherapeutic treatments. Thus, our work spans animal models of addiction at the level of molecular physiology and morphology to strong clinical collaborations conducting clinical trials in human addicts. We focus on the long-lasting changes in brain function produced by drug use and a single strong stress that create the enduring vulnerability to environmental cues producing relapse to drug use or stress-associated behaviors. In the course of the last 15-20 years of research we have come to a conclusion that impairments in how the prefrontal cortex regulates motivational circuitry in the striatum are a critical drug- and stress-induced pathology. Accordingly, much of our work focuses on how addictive drugs and stress regulate glutamatergic neurotransmission and synaptic plasticity in the nucleus accumbens (the brain portal whereby prefrontal cortex initiates behavioral change and adaptation), and on accumbens projections to the ventral pallidum and its downstream targets.  Importantly, while we quantify classic synaptic physiology and morphology, we have come to the conclusion that critical adaptions conferring vulnerability to relapse and the intensity of the drug seeking or stress responding are to be found in perisynaptic astroglia and extracellular matrix, that together with the pre- and postsynapse for a homeostatic compartment referred to as the tetrapartite synapse.