Abstract
SUMMARYHere, 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.
Highlights
The paraventricular thalamus (PVT) has been recently identified as a key component in the neural circuitry of drug addiction in both humans and rodents (Huang et al, 2018; McGinty and Otis, 2020; Zhou et al, 2021; Zhou and Zhu, 2019)
We found that optogenetic activation of the PVT/nucleus accumbens (NAc) pathway is capable of inducing aversion in animals with a heroin self-administration history, but only after abstinence and not extinction
Optogenetic activation of the PVT/NAc pathway drives aversion and heroin relapse First, we investigated whether optogenetic activation of the PVT/NAc pathway was capable of driving real-time conditioned place aversion (rtCPA) in naive animals
Summary
The paraventricular thalamus (PVT) has been recently identified as a key component in the neural circuitry of drug addiction in both humans and rodents (Huang et al, 2018; McGinty and Otis, 2020; Zhou et al, 2021; Zhou and Zhu, 2019). Two of the most commonly used models of this type employ either a period of home cage abstinence during drug withdrawal or extinction training (Reiner et al, 2019; Venniro et al, 2016). The central nucleus of the amygdala is critical for relapse after abstinence (Venniro et al, 2017, 2020), whereas the prefrontal cortex is recruited by extinction learning to regulate subcortical targets that drive drug seeking (Peters et al, 2009)
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