Assessing the Role of Corticothalamic and Thalamo-Accumbens Projections in the Augmentation of Heroin Seeking in Chronically Food-Restricted Rats

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 foodrestricted rats compared with 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 corticothalamic 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 d. Next, rats were removed from the self-administration chambers and were subjected to a 14 d 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 h heroin-seeking test under extinction conditions during which corticothalamic and thalamo-accumbens neural activity was altered using chemogenetics. Surprisingly, chemogenetic activation or inhibition of corticothalamic projections did not alter heroin-seeking behavior. 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.

Functional Connectivity of the Human Paraventricular Thalamic Nucleus: Insights From High Field Functional MRI

“…In humans, major depression and its symptom severity have been linked with increased functional connectivity between the medial thalamus and cortical areas (Brown et al, 2017). In addition to PVT recruitment to natural rewards, the PVT has also be implicated in drug seeking behaviors and addiction (Matzeu et al, 2014;Chisholm et al, 2021).…”

Reduced thalamic resting‐state functional connectivity and impaired cognition in acute abstinent heroin users

“…Animal studies had been focused on paraventricular (PVT) of thalamus, a part of the midline and intralaminar thalamus of rats (Parsons, Li, & Kirouac, 2007), in mediating associations between drug and drug‐related cues (Huang et al, 2018). PVT neuron was activated after the reinstatement of drug‐seeking behavior, while the activation abolished heroin‐seeking in chronically food‐restricted rats (Chisholm et al, 2020). PVT orchestrated the maintenance of opiate‐associated memories via projections to the NAc (Keyes et al, 2020).…”

Thalamo-Nucleus Accumbens Projections in Motivated Behaviors and Addiction

“…Finally, two studies also linked drug-seeking behavior to the hunger state of the animal, by showing that chronic foodrestriction increased heroin-seeking behavior after withdrawal from self-administration. This phenomenon was modulated by PVT = > NAc shell neurons, as their enhanced activity attenuated this food restriction-induced heroin seeking (Chisholm et al, 2020(Chisholm et al, , 2021, demonstrating an overlap between PVT = > NAc circuits driving food-and drug-seeking behaviors.…”