The role of ghrelin in drug and natural reward

Vengeliene, Valentina

doi:10.1111/adb.12114

Cited by 28 publications

(16 citation statements)

References 34 publications

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“…Leptin has been shown to be involved in energy homeostasis and stress; 30 however, emerging evidence has shown that structural and functional changes in the mesolimbic reward system are associated with reward-related behaviors, which involve hormonal regulators such as leptin, ghrelin and insulin. 31 , 32 In this study, the effects of endogenous leptin signaling on cocaine reward-associated behaviors and anxiety were detected. We found that downregulation of leptin signaling in the VTA and NAc enhanced the acquisition of cocaine-CPP, while upregulation of leptin signaling induced the opposite effect.…”

Section: Discussionmentioning

confidence: 88%

Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

et al. 2016

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The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure. Our results showed that inhibition of leptin signaling by intracerebroventricular infusion of the leptin receptor (LepR) antagonist SMLA during cocaine conditioning increased the cocaine-CPP and upregulated the level of dopamine and its metabolites in the nucleus accumbens (NAc). We then selectively knocked down the LepR in the mesolimbic ventral tegmental area (VTA), NAc core and central amygdala (CeA) by injecting AAV-Cre into Leprflox/flox mice. LepR deletion in the VTA increased the dopamine levels in the NAc and enhanced the cocaine-conditioned reward. LepR deletion in the NAc core enhanced the cocaine-conditioned reward and impaired the effect of the D2-dopamine receptor on cocaine-CPP, whereas LepR deletion in the CeA had no effect on cocaine-CPP but increased the anxiety level of mice. In addition, prior exposure to saccharin increased LepR mRNA and STAT3 phosphorylation in the NAc and VTA and impaired cocaine-CPP. These results indicate that leptin signaling is critically involved in cocaine-conditioned reward and the regulation of drug reward by a natural reward and that these effects are dependent on mesolimbic LepR.

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Section: Discussionmentioning

confidence: 88%

Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward

et al. 2016

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“…In this system, dopamine acts as a marker molecule for incentive sensitization and the dopaminergic neurons represent the locus of action for addictive compounds (Berridge & Robinson ). More recently, it has been postulated that a modulation of the ghrelin pathway also affects drug‐seeking behavior (for an overview: Vengeliene ).…”

Section: Introductionmentioning

confidence: 99%

Ghrelin modulates mesolimbic reactivity to alcohol cues in alcohol‐addicted subjects: a functional imaging study

et al. 2018

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Ghrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self-administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol-addicted subjects. We included 41 recently detoxified alcohol-dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol-related pictures. Additionally, we assessed patients' alcohol craving using the Alcohol Urge Questionnaire and a visual analogue scale. Plasma concentrations of total and acylated (activated) ghrelin were measured in parallel to the fMRI session. The association between ghrelin plasma concentrations, mesolimbic cue reactivity and alcohol craving was assessed by performing correlation and mediation analyses. Alcohol-induced brain response in a network of brain clusters, including the right and left ventral striatum, showed a significant positive association with acylated ghrelin plasma concentration. Additionally, acylated ghrelin was significantly associated with craving. Mediation analyses showed that the association between acylated ghrelin plasma concentration and alcohol craving is mediated by a cue-induced brain response in the ventral striatum. Based on the finding that ghrelin modulates mesolimbic reactivity to alcohol cues, the following should be considered: If alcohol craving and the appetitive status were interrelated, this has to be taken into account when implementing fMRI studies for addictive disorders. Moreover, appetite regulation seems to represent a valid treatment target for reducing cue reactivity in addictive disorders.

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“…Especially for addictive disorders an involvement of ghrelin has been repeatedly shown (Jerlhag et al, 2006(Jerlhag et al, , 2007Vengeliene, 2013) and ghrelin's role in mood and anxiety disorders , neurodegenerative diseases (Frago et al, 2002;Gahete et al, 2011) and eating disorders (Otto et al, 2001;Atalayer et al, 2013) is being increasingly elucidated. Several reviews have recently been published on ghrelin in addictive disorders (Andrews, 2011;Dickson et al, 2011;Leggio et al, 2011;Vengeliene, 2013;Panagopoulos and Ralevski, 2014), neurodegenerative diseases (Andrews, 2011;Gahete et al, 2011;Dos Santos et al, 2013), mood disorders Andrews, 2011;Schellekens et al, 2012) and eating disorders (Atalayer et al, 2013;Méquinion et al, 2013;Monteleone and Maj, 2013). However, there is no review so far summarizing the role of ghrelin in psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%