The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice

Jerlhag, Elisabet; Landgren, Sara; Egecioglu, Emil; Dickson, Suzanne L.; Engel, Jörgen A.

doi:10.1016/j.alcohol.2010.10.002

Cited by 84 publications

(45 citation statements)

References 62 publications

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“…Indeed, SNPs and haplotypes of both the pro-ghrelin and GHS-R1A genes have been associated with increased weight in alcohol dependent individuals (Landgren et al 2008). Central ghrelin signalling has over the last years been shown to mediate the reward from alcohol Jerlhag et al 2010b), cocaine, amphetamine (Jerlhag et al 2010a;Wellman et al 2005;Tessari et al 2007), and palatable/rewarding food Perello et al 2010;Skibicka et al 2011a;Skibicka et al 2011b). Collectively these studies imply that central ghrelin signalling, including the GHS-R1A may constitute a novel target for development of treatment strategies for addictive behaviours.…”

Section: Discussionmentioning

confidence: 94%

The role of the central ghrelin system in reward from food and chemical drugs

Dickson

Egecioglu

Landgren

et al. 2011

Molecular and Cellular Endocrinology

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Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergicdopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA

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Section: Discussionmentioning

confidence: 94%

The role of the central ghrelin system in reward from food and chemical drugs

Dickson

Egecioglu

Landgren

et al. 2011

Molecular and Cellular Endocrinology

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215

167

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“…The ability of alcohol to induce a locomotor stimulation, dopamine release and conditioned place preference is reduced in ghrelin knockout mice (Jerlhag et al., 2011), implying that either centrally or peripherally produced ghrelin is of importance for alcohol reinforcement. The findings that IP injections of ghrelin does not alter alcohol intake in alcohol‐naïve rats (Lyons et al., 2008), that ghrelin is produced centrally (Cowley et al., 2003; Lu et al., 2002; Mondal et al., 2005), and that NOX‐B11‐2 does not alter alcohol reinforcement collectively suggest that centrally, rather than peripherally, produced ghrelin is of importance for alcohol intake and alcohol reward in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, it was shown that ghrelin activates cholinergic‐dopaminergic reward link (Abizaid et al., 2006; Jerlhag et al., 2006a, 2007). This was corroborated by the finding showing that the rewarding properties of alcohol, as measured by locomotor stimulation, accumbal dopamine release, and conditioned place preference are attenuated in mice with suppressed GHS‐R1A and ghrelin signaling (Jerlhag et al., 2009, 2011) and that GHS‐R1A antagonists reduced the intake and the motivation to consume alcohol in rodents (Jerlhag et al., 2009; Kaur and Ryabinin, 2010; Landgren et al., 2012). Supportively, human genetic findings show that a single‐nucleotide polymorphism in the GHS‐R1A gene is associated with high alcohol consumption in humans (Landgren et al., 2008).…”

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confidence: 99%

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Jerlhag

Ivanoff

Vater

et al. 2014

Alcoholism Clin & Exp Res

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BackgroundDevelopment of alcohol dependence, a chronic and relapsing disease, largely depends on the effects of alcohol on the brain reward systems. By elucidating the mechanisms involved in alcohol use disorder, novel treatment strategies may be developed. Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor 1A, acts as an important regulator of energy balance. Recently ghrelin and its receptor were shown to mediate alcohol reward and to control alcohol consumption in rodents. However, the role of central versus peripheral ghrelin for alcohol reward needs to be elucidated.MethodsGiven that ghrelin mainly is produced by peripheral organs, the present study was designed to investigate the role of circulating endogenous ghelin for alcohol reward and for alcohol intake in rodents.ResultsWe showed that the Spiegelmer NOX‐B11‐2, which binds and neutralizes acylated ghrelin in the periphery with high affinity and thus prevents its brain access, does not attenuate the alcohol‐induced locomotor activity, accumbal dopamine release and expression of conditioned place preference in mice. Moreover, NOX‐B11‐2 does not affect alcohol intake using the intermittent access 20% alcohol 2‐bottle‐choice drinking paradigm in rats, suggesting that circulating ghrelin does not regulate alcohol intake or the rewarding properties of alcohol. In the present study, we showed however, that NOX‐B11‐2 reduced food intake in rats supporting a role for circulating ghrelin as physiological regulators of food intake. Moreover, NOX‐B11‐2 did not affect the blood alcohol concentration in mice.ConclusionsCollectively, the past and present studies suggest that central, rather than peripheral, ghrelin signaling may be a potential target for pharmacological treatment of alcohol dependence.

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“…This finding was abolished by pretreatment with gammabutyrolactone, an agent which blocks dopamine firing and dopamine release (Di Chiara and Imperato 1988;Imperato and Di Chiara 1986). In addition, voluntary oral ethanol self-administration in alcohol-preferring Wistar rats has shown a robust increase of extracellular dopamine levels in the NAc with maximal effects at approximately 15-30 min after peak intake (Blanchard et al 1993;Bustamante et al 2008;Jerlhag et al 2011;Kiianmaa et al 1995;Nurmi et al 1998;Weiss et al 1993), suggesting that dopaminergic neurotransmission in the NAc may be an important factor in alcohol reinforcement. Also, the dopamine transporter together with dopamine innervation density, as determined by tyrosine hydroxylase immunostaining, was found to be lower in the NAc of the ethanol-preferring compared with that of non-preferring rats (Casu et al 2002a, b;Zhou et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

Bahí

Dreyer

2012

Psychopharmacology

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Rationale Dopamine D1 receptor (D1R) signaling has been associated to ethanol consumption and reward in laboratory animals. Objectives Here, we hypothesize that this receptor, which is located within the nucleus accumbens (NAc) neurons, modulates alcohol reward mechanisms. Methods To test this hypothesis, we measured alcohol consumption and ethanol-induced psychomotor sensitization and conditioned place preference (CPP) in mice that received bilateral microinjections of small interference RNA (siRNA)-expressing lentiviral vectors (LV-siD1R) producing D1R knock-down. The other group received control (LV-Mock) viral vectors into the NAc. Results There were no differences in the total fluid consumed and also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the LV-siD1R group consumed less ethanol than the control group. This difference was not associated to taste neophobia. In addition, results have shown that downregulation of endogenous D1R using viral-mediated siRNA in the NAc significantly decreased ethanol-induced behavioral sensitization as well as acquisition, but not expression, of ethanol-induced place preference.Conclusions We conclude that decreased D1R expression into the NAc led to reduced ethanol rewarding properties, thereby leading to lower voluntary ethanol consumption. Together, these findings demonstrate that the D1 receptor pathway within the NAc controls ethanol reward and intake.

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The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice

Cited by 84 publications

References 62 publications

The role of the central ghrelin system in reward from food and chemical drugs

The role of the central ghrelin system in reward from food and chemical drugs

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

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