Brain Regions Related to Tool Use and Action Knowledge Reflect Nicotine Dependence

Abstract

In addition to reward-and craving-related processes, habitual mechanisms play an important role in addiction. While the dorsal striatum has been proposed to code for the motivational state of habitual drug-seeking actions, the neural underpinnings of the corresponding drug-taking skills and action knowledge remain poorly understood. We used functional magnetic resonance imaging (fMRI) and a behavioral orientation affordance paradigm to investigate the neural and behavioral correlates of automatized drug-taking actions in nicotine dependence. Smokers exhibited higher fMRI activations than nonsmokers when viewing smoking-related but not when viewing control images. These group differences in fMRI activations were located not only in brain regions associated with craving and habitual learning (left ventral and dorsal striatum, dorsolateral prefrontal cortex, insula, uncus, medial frontal gyrus, right subcallosal gyrus, and bilateral parahippocampal gyrus), but also in a network of brain regions which has been strongly implicated in the encoding of action knowledge and tool use skills (bilateral premotor cortex, left superior parietal lobule, and right lateral cerebellum). A behavioral affordance reaction-time task indicated that smokers, but not nonsmokers, showed an automatized responsiveness to smoking paraphernalia similar to everyday objects. Moreover, smokers showed strong intercorrelations between fMRI activations in tool use-related brain regions, behavioral responsiveness to smoking-related cues, and severity of nicotine dependence. Apparently smoking-related action representations in smokers are stored in brain regions typically representing tool use skills and action knowledge. Most importantly, cortical and behavioral correlates of the respective drug-taking skills vary with the individual degree of nicotine dependence.

Chronic Nicotine Treatment Impacts the Regulation of Opioid and Non-opioid Peptides in the Rat Dorsal Striatum

“…Our results, obtained after 13 weeks of nicotine administration, are consistent with previous reports of elevated Met-enkephalin in the striatum following nicotine treatment for periods of 2 weeks, which was measured using immunoassay (15). These results parallel the persistent activation of the DS during long term nicotine exposure or the preoccupation/craving stage of drug dependence (5,45), and the results further support a close functional link between dopamine and enkephalin systems, which are both under the regulation of nicotine (46). Enhancements of the remaining three PENK peptides have not been previously reported and suggest a broader involvement of the PENK pathway than has not been previously uncovered using immunoassay.…”

“…This suggests that the increase of these peptides may reflect elevated precursor synthesis, consistent with the elevated preproenkephalin mRNA levels in the striatum after chronic nicotine application (15). Another class of opioid peptides, dynorphins derived from PDYN including dynorphin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) and dynorphin(1-8), was not modulated by chronic nicotine. This is consistent with previous literature linking PDYN peptides to aversive states associated with drug withdrawal (47), which were not induced in our experiment.…”

“…Compared with the brain regions associated with reward-and cravingrelated processes (6), the DS is a core brain center associated with habitual mechanisms, which are important for the later stage of drug dependence (52). Indeed, an increasing body of evidence has shown that the DS is involved in compulsive and automatic drug-taking (5,52). Our neuropeptidomics study pro-vides a comprehensive investigation on the peptide changes of the DS under the long-period challenging of nicotine.…”

“…The dorsal striatum (DS) 1 is one of the key brain regions that has been associated with neural regulation during chronic nicotine exposure (5). In particular, the DS is involved in habit formation during the preoccupation/craving (later) phase of nicotine dependence characterized by compulsive drug-taking (6).…”

The motor way: Clinical implications of understanding and shaping actions with the motor system in autism and drug addiction

“…3 Drug use, drug abuse, and drug dependence: three consecutive but independent phases with increasing severity. Low-order cue reactivity (CR) plays a potential role in drug-seeking and drug-taking behavior (gray boxes and color lines are the parts specifically considered in this study) a role in the low-order CR phenomenon (Brody et al, 2002;Kosten et al, 2006;Smolka et al, 2006;Wagner, Dal Cin, Sargent, Kelley, & Heatherton, 2011;Yalachkov, Kaiser, & Naumer, 2009) (see Fig. 3).…”