The Neurobiology of Addiction Research Center (NARC)
Project 1 – Synpatic Plasticity Regulating Cocaine relapse
Principle Investigator: Peter Kalivas, Ph.D.
Co-Principle Investigator: Antonieta Lavin, Ph.D.
Activation of the glutamatergic projection from the prelimbic prefrontal cortex (PFC) to the core of the nucleus accumbens (NAcore) is associated with the initiation of learned, motivated behavior. In animals trained to self-administer cocaine and then placed in extinction training, this projection is necessary to initiate drug-seeking in several reinstatement models of relapse. Correspondingly, a number of enduring changes in NAcore neuron morphology, protein content and electrophysiological properties have been demonstrated in animals withdrawn from repeated cocaine administration. Interestingly, neuroadaptive changes produced in animals that have undergone extinction training during withdrawal from cocaine self-administration may differ from animals placed in abstinence for the same withdrawal period. This view is buttressed by discoveries made by the Neurobiology of Addiction Research Center (NARC) that support the presence of important and often distinct behavioral and protein effects on PFC inputs to the accumbens by explicit extinction training versus abstinence from the drug context during withdrawal. Together, these data predict the two overarching hypotheses of Project 1. 1) Neuroadaptations in PFC excitatory efferents to the NAcore are critical for the initiation of drug-seeking in cocaine-trained animals. 2) Extinction training and abstinence induce distinct effects on protein, morphological and electrophysiological measures of excitatory plasticity in the accumbens.
As part of investigating these hypotheses, Project 1 has discovered marked electrophysiological and morphological adaptations in the nucleus accumbens that are associated with the induction of relapse or produced by placing cocaine addicted animals into an extinguished environment.