Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in "relapse prone" male rats.

Autor: Kuhn BN; Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA., Campus P; Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA., Klumpner MS; Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA., Chang SE; Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA., Iglesias AG; Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA., Flagel SB; Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI, 48109, USA. sflagel@umich.edu.; Michigan Neuroscience Institute, University of Michigan, 205 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. sflagel@umich.edu.; Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI, 48105, USA. sflagel@umich.edu.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2022 Apr; Vol. 239 (4), pp. 1035-1051. Date of Electronic Publication: 2021 Jun 28.
DOI: 10.1007/s00213-021-05894-9
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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