Cholinergic Functioning in Stimulant Addiction

Sofuoglu, Mehmet; Mooney, Marc E

doi:10.2165/11310920-000000000-00000

Cited by 64 publications

(32 citation statements)

References 103 publications

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“…Based on this work, it has been suggested that the cholinergic system be targeted in treating nicotine and other drug addiction [34,35,45]. Preclinical experiments support this idea.…”

Section: Mesolimbic Ach Projections and Inputsmentioning

confidence: 79%

“…In order to discuss the overlaps that may exist between overeating and drug addiction as they relate to ACh, in this section, we will very briefly discuss the effects that cholinergic neurons have on the intake of drugs of abuse. For more comprehensive reviews on this topic, see Williams and Adinoff [34] and Sofuogu and Mooney [35]. …”

Section: Mesolimbic Ach Projections and Inputsmentioning

confidence: 99%

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Cholinergic modulation of food and drug satiety and withdrawal

Avena

Rada

2012

Physiology & Behavior

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Although they comprise only a small portion of the neurons in the region, cholinergic interneurons in the dorsal striatum appear to play an important role in the regulation of various appetitive behaviors, in part, through their interactions with mesolimbic dopamine (DA) systems. In this review, we describe studies that suggest that the activity of cholinergic interneurons in the nucleus accumbens (NAc) and cholinergic projections to the ventral tegmental area (VTA) affect feeding behavior. In vivo microdialysis studies in rats have revealed that the cessation of a meal is associated with a rise in acetylcholine (ACh) levels in the NAc. ACh activation will suppress feeding, and this is also associated with an increase in synaptic accumulation of ACh. Further, we discuss how, in addition to their role in the ending of a meal, cholinergic interneurons in the NAc play an integral role in the cessation of drug use. Another cholinergic system involved in different aspects of appetitive behavior is the projection from the pedunculpontine nuclei directly to the VTA. Activation of this system enhances behaviors through activation of the mesolimbic DA system, and antagonism of ACh receptors in the VTA can reduce drug self-administration. Finally, we discuss the role of accumbens ACh in both drug and palatable food withdrawal. Studies reveal that accumbens ACh is increased during withdrawal from several different drugs of abuse (including cocaine, nicotine and morphine). This rise in extracellular levels of ACh, coupled with a decrease in extracellular levels of DA, is believed to contribute to an aversive state, which can manifest as behaviors associated with drug withdrawal. This theory has also been applied to studies of overeating and/or “food addiction,” and the findings suggest a similar imbalance in DA/ACh levels, which is associated with behavioral indications of drug-like withdrawal. In summary, cholinergic neurons play an important role in the modulation of both food and drug intake, as well as the aversive aspects of food- and drug-related addictive behaviors.

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“…Based on this work, it has been suggested that the cholinergic system be targeted in treating nicotine and other drug addiction [34,35,45]. Preclinical experiments support this idea.…”

Section: Mesolimbic Ach Projections and Inputsmentioning

confidence: 79%

Section: Mesolimbic Ach Projections and Inputsmentioning

confidence: 99%

Cholinergic modulation of food and drug satiety and withdrawal

Avena

Rada

2012

Physiology & Behavior

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“…Rats that are prone to attribute incentive salience to reward cues (“sign trackers”), relative to “goal-trackers”, are vulnerable to developing obesity and addiction (Paolone et al, 2013). Because of its interaction of the limbic reward and prefrontal cognitive control circuits, cholinergic neurotransmission has been a target for pharmacotherapy development for stimulant addiction (Sofuoglu and Mooney, 2009). Thus, the current findings of the systems level functional connectivity of the BNM will help future studies to pursue the etiology and treatment of addiction on these related fronts.…”

Section: Discussionmentioning

confidence: 99%

Resting state functional connectivity of the basal nucleus of Meynert in humans: In comparison to the ventral striatum and the effects of age

Ide

Zhang

et al. 2014

NeuroImage

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The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer’s disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.

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“…These medications increase the synaptic concentrations of acetylcholine (ACh), resulting in increased acetylcholine transmission. Acetylcholine mediates many cognitive functions including attention, working memory, motivation, and reward (Mark, Shabani, Dobbs, & Hansen, 2011; Sarter, Lustig, Howe, Gritton, & Berry, 2014; Sofuoglu & Mooney, 2009), and its release in the prefrontal cortex is especially relevant for attentional functions (Howe, Berry, Francois, Gilmour, Carp, Tricklebank, Lustig, & Sarter, 2013). Two cholinesterase inhibitors, galantamine and rivastigmine, showed promising results in pilot studies for stimulant use disorder (Mahoney et al, 2014; Sofuoglu & Carroll, 2011).…”

Section: Treatment Approaches Targeting Cognitive Functionsmentioning

confidence: 99%

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders

Sofuoglu

DeVito

Waters

et al. 2016

Journal of Dual Diagnosis

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Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancements to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies.

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Cholinergic Functioning in Stimulant Addiction

Cited by 64 publications

References 103 publications

Cholinergic modulation of food and drug satiety and withdrawal

Cholinergic modulation of food and drug satiety and withdrawal

Resting state functional connectivity of the basal nucleus of Meynert in humans: In comparison to the ventral striatum and the effects of age

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders

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