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Assessing the role of cortico-thalamic and thalamo-accumbens projections in the augmentation of heroin seeking in chronically food-restricted rats.

J Neurosci. 2020 Nov 20; :

Authors: Chisholm A, Rizzo D, Fortin É, Moman V, Quietshat N, Romano A, Capolicchio T, Shalev U

Abstract

Drug addiction is a chronic disorder characterized by compulsive drug seeking and involves repetitive cycles of compulsive drug use, abstinence, and relapse. In both human and animal models of addiction, chronic food restriction increases rates of relapse. Our laboratory has reported a robust increase in drug-seeking following a period of withdrawal in chronically food-restricted rats compared to sated controls. Recently, we reported that activation of the paraventricular nucleus of the thalamus (PVT) abolished heroin seeking in chronically food-restricted rats. However, the precise inputs and outputs of the PVT that mediate this effect remain elusive. The goal of the current study was to determine the role of cortico-thalamic and thalamo-accumbens projections in the augmentation of heroin seeking induced by chronic food restriction. Male Long-Evans rats were trained to self-administer heroin for 10 days. Next, rats were removed from the self-administration chambers and were subjected to a 14-day withdrawal period while sated (unlimited access to food) or mildly food-restricted (FDR). On day 14, rats were returned to the self-administration context for a 3-hr heroin-seeking test under extinction conditions during which cortico-thalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of cortico-thalamic projections did not alter heroin seeking behaviour. Chemogenetic activation of thalamo-accumbens shell, but not core, projectors attenuated heroin seeking in FDR rats. The results indicate an important role for the PVT to nucleus accumbens shell projections in the augmentation of heroin seeking induced by chronic food restriction.SIGNIFICANCE STATEMENTRelapse to heroin use is one of the major obstacles in the treatment of opiate addiction. Triggers for relapse are modulated by environmental challenges such as caloric restriction. Elucidating the brain mechanisms that underlie relapse is critical for evidence-based treatment development. Here we demonstrate a critical role for the input from the paraventricular thalamus (PVT), a hub for cortical, sensory and limbic information, to the nucleus accumbens shell (an area known to be important for reward and motivation) in the augmentation of heroin seeking in food-restricted rats. Our findings highlight a previously unknown role for the PVT in heroin seeking following a period of abstinence.

PMID: 33219004 [PubMed - as supplied by publisher]