Aversive stimuli and loss in the mesocorticolimbic dopamine system

Brooks, Andrew M.; Berns, Gregory S.

doi:10.1016/j.tics.2013.04.001

Cited by 73 publications

(57 citation statements)

References 78 publications

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“…Electrophysiological experiments have found evidence for the existence of two separated populations of dopamine neurons that respond differently to aversive stimuli. Most dopamine cells respond by decreasing their activity and these are cells that also increase their firing upon presentation of rewarding stimuli or with the termination of an aversive stimulus (Brooks and Berns, 2013; Abraham et al, 2014). The other subpopulation increases its activity upon presentation of an aversive stimulus and it seems to be specifically localized in the most medial and posterior part of the ventral tegmental area (pmVTA; Brooks and Berns 2013; Abraham et al 2014; Lammel et al 2014).…”

Section: Wise and Bozarth’s Psychomotor Stimulant Theory Of Addictionmentioning

confidence: 99%

“…Most dopamine cells respond by decreasing their activity and these are cells that also increase their firing upon presentation of rewarding stimuli or with the termination of an aversive stimulus (Brooks and Berns, 2013; Abraham et al, 2014). The other subpopulation increases its activity upon presentation of an aversive stimulus and it seems to be specifically localized in the most medial and posterior part of the ventral tegmental area (pmVTA; Brooks and Berns 2013; Abraham et al 2014; Lammel et al 2014). In fact, this area projects to a specific striatal area, also the posteriomedial part of the shell of the nucleus accumbens (pmNAc shell; Vertes 2004; Quiroz et al 2015), specifically involved in threat-related behaviors (Richard et al 2013).…”

Section: Wise and Bozarth’s Psychomotor Stimulant Theory Of Addictionmentioning

confidence: 99%

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Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

2016

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Background The psychostimulant properties of caffeine are reviewed and compared with those of prototypical psychostimulants, able to cause substance use disorders (SUD). Caffeine produces psychomotor activating, reinforcing and arousing effects, which depend on its ability to disinhibit the brake that endogenous adenosine imposes on the ascending dopamine and arousal systems. Objectives A model that considers the striatal adenosine A2A-dopamine D2 receptor heteromer as a key modulator of dopamine-dependent striatal functions (reward-oriented behavior and learning of stimulus-reward and reward-response associations) is introduced, which should explain most of the psychomotor and reinforcing effects of caffeine. Highlights The model can explain the caffeine-induced rotational behavior in rats with unilateral striatal dopamine denervation and the ability of caffeine to reverse the adipsic-aphagic syndrome in dopamine-deficient rodents. The model can also explain the weaker reinforcing effects and low abuse liability of caffeine, compared with prototypical psychostimulants. Finally the model can explain the actual major societal dangers of caffeine: the ability of caffeine to potentiate the addictive and toxic effects of drugs of abuse, with the particularly alarming associations of caffeine (as adulterant) with cocaine, amphetamine derivatives and synthetic cathinones and energy drinks with alcohol; and the higher sensitivity of children and adolescents to the psychostimulants effects of caffeine and its possible increase in the vulnerability to develop SUD. Conclusions The striatal A2A-D2 receptor heteromer constitutes an unequivocal main pharmacological target of caffeine and provides the main mechanisms by which caffeine potentiates the acute and long-term effects of prototypical psychostimulants.

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Section: Wise and Bozarth’s Psychomotor Stimulant Theory Of Addictionmentioning

confidence: 99%

Section: Wise and Bozarth’s Psychomotor Stimulant Theory Of Addictionmentioning

confidence: 99%

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

2016

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“…Thus, dopamine release encodes the expectation of a reward, and responds with a spike if the reward is better than expected and with a dip if it is worse [142]. Interestingly, dopamine is released by separate VTA neurons when unpleasant or aversive stimuli are encountered [143]. In humans, recent work suggests dopamine release reflects the confidence that a chosen behavior will lead to an expected outcome [144].…”

Section: Actions In Reward Pathwaysmentioning

confidence: 99%

The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances

Hill

Faulkner²

2016

Neuroendocrinology

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Obesity is increasing in prevalence across all sectors of society, and with it a constellation of associated ailments including hypertension, type 2 diabetes, and eating disorders. The melanocortin system is a critical neural system underlying the control of body weight and other functions. Deficits in the melanocortin system may promote or exacerbate the comorbidities of obesity. This system has therefore generated great interest as a potential target for treatment of obesity. However, drugs targeting melanocortin receptors are plagued by problematic side effects, including undesirable increases in sympathetic nervous system activity, heart rate, and blood pressure. Circumnavigating this roadblock will require a clearer picture of the precise neural circuits that mediate the functions of melanocortins. Recent, novel experimental approaches have significantly advanced our understanding of these pathways. We here review the latest advances in our understanding of the role of melanocortins in food intake, reward pathways, blood pressure, glucose control, and energy expenditure. The evidence suggests that downstream melanocortin-responsive circuits responsible for different physiological actions do diverge. Ultimately, a more complete understanding of melanocortin pathways and their myriad roles should allow treatments tailored to the mix of metabolic disorders in the individual patient.

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“…Notably, TLR4 can be activated directly by opioids [19] and cocaine [20], and this activation contributes to drug reinforcement via increasing the level of extracellular dopamine (DA) in the nucleus accumbens (NAc) [20]. It is well established that the mesolimbic DA system is closely associated with approach-avoidance behavior [21,22]. We thus hypothesized that TLR4 signaling might play a critical role in mediating this behavior.…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Yan

Cheng

et al. 2016

Neurosci. Bull.

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Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4 -/-) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4 -/-mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4 -/-mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approachavoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4 -/-mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4 -/-mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4 -/-mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.

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Aversive stimuli and loss in the mesocorticolimbic dopamine system

Cited by 73 publications

References 78 publications

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

The Role of the Melanocortin System in Metabolic Disease: New Developments and Advances

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

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