Brittany N Kuhn1, Paolo Campus2, Marin S Klumpner2, Stephen E Chang2, Amanda G Iglesias1, Shelly B Flagel3,4,5. 1. Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. 2. Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. 3. Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. sflagel@umich.edu. 4. Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. sflagel@umich.edu. 5. Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48105, USA. sflagel@umich.edu.
Abstract
RATIONALE: Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. OBJECTIVES: The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether "top-down" cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. RESULTS: Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype-locomotor response to novelty-inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. CONCLUSIONS: These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is consequent to individual differences in the propensity to attribute incentive salience to discrete reward cues.
RATIONALE: Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. OBJECTIVES: The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether "top-down" cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. RESULTS: Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype-locomotor response to novelty-inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. CONCLUSIONS: These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is consequent to individual differences in the propensity to attribute incentive salience to discrete reward cues.
Authors: Ana-Clara Bobadilla; Jasper A Heinsbroek; Cassandra D Gipson; William C Griffin; Christie D Fowler; Paul J Kenny; Peter W Kalivas Journal: Prog Brain Res Date: 2017-10-12 Impact factor: 2.453
Authors: Brittany N Kuhn; Nazzareno Cannella; Ayteria D Crow; Analyse T Roberts; Veronica Lunerti; Carter Allen; Rusty W Nall; Gary Hardiman; Leah C Solberg Woods; Dongjun Chung; Roberto Ciccocioppo; Peter W Kalivas Journal: Psychopharmacology (Berl) Date: 2022-09-16 Impact factor: 4.415