Extinction blunts paraventricular thalamic contributions to heroin relapse
Giuseppe Giannotti,
Sheng Gong,
Nicholas Fayette,
Jasper A. Heinsbroek,
James E. Orfila,
Paco S. Herson,
Christopher P. Ford,
Jamie Peters
Affiliations
Giuseppe Giannotti
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Sheng Gong
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Nicholas Fayette
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Jasper A. Heinsbroek
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
James E. Orfila
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Paco S. Herson
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Christopher P. Ford
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Jamie Peters
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding author
Summary: Here, we use optogenetics and chemogenetics to investigate the contribution of the paraventricular thalamus (PVT) to nucleus accumbens (NAc) pathway in aversion and heroin relapse in two different heroin self-administration models in rats. In one model, rats undergo forced abstinence in the home cage prior to relapse testing, and in the other, they undergo extinction training, a procedure that is likened to cognitive behavioral therapy. We find that the PVT→NAc pathway is both sufficient and necessary to drive aversion and heroin seeking after abstinence, but not extinction. The ability of extinction to reduce this pathway’s contribution to heroin relapse is accompanied by a loss of synaptic plasticity in PVT inputs onto a specific subset of NAc neurons. Thus, extinction may exert therapeutic reductions in opioid seeking by altering synaptic plasticity within the PVT→NAc pathway, resulting in reduced aversion during opioid withdrawal as well as reduced relapse propensity.
