The thalamus in drug addiction: from rodents to humans

Abstract

Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks. Findings from the animal literature suggest that the paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal nucleus may be involved in the reinstatement, extinction and expression of drug-seeking behaviours. In support of the iRISA model, the human addiction imaging literature demonstrates enhanced thalamus activation when reacting to drug cues and reduced thalamus activation during response inhibition. This pattern of response was further associated with the severity of, and relapse in, drug addiction. Future animal studies could widen their field of focus by investigating the specific role(s) of different thalamic nuclei in different phases of the addiction cycle. Similarly, future human imaging studies should aim to specifically delineate the structure and function of different thalamic nuclei, for example, through the application of advanced imaging protocols at higher magnetic fields (7 Tesla).This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.

Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the Social Incentive Delay task

“…Therefore, the involvement of the insula during the anticipation of social rewards and punishment avoidance in the SID task is compatible with an overall role of the insula in the autonomic activation (arousal) associated with the anticipation of salient social incentives (Schneider et al, 2018). The thalamus encodes an alerting signal to respond to salient stimuli (Wolff and Vann, 2019;Zhu et al, 2018) by conveying interoceptive information from the insula to the striatum, where an appropriate action response is then selected (Huang et al, 2018). Interestingly, social cognition impairments have been reported in stroke patients with unilateral thalamic lesions (Wilkos et al, 2015).…”

Common and separable neural alterations in substance use disorders: evidence from coordinate-based meta-analyses of functional neuroimaging studies in human

“…The thalamus exhibits particularly high expressions of nicotine-sensitive receptors in the brain, which may partly contribute to the nicotine-specific alterations observed in this region [158], [159]. This nicotine-specific finding may reflect that in addition to striatal reward-related dysregulations nicotine use induced neuroadaptations in the thalamic circuit play an important role and may promote response inhibition impairments observed in both, animal and human models of nicotine addiction [160].…”

Heroin addiction engages negative emotional learning brain circuits in rats

“…As part of a habit-learning circuit, the thalamus and dorsal striatum are implicated in reward and incentive salience (2,25). Additionally, the naloxone-paired cue activated the precommissural nucleus (PRC), periaqueductal gray (PAG)/periventricular gray (PVG), and the pretectal nucleus in LgA rats, whereas these same regions were deactivated in ShA rats.…”