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

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

doi:10.1016/j.mce.2011.02.017

Cited by 217 publications

(185 citation statements)

References 123 publications

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“…Recent studies have implicated ghrelin and the GHS-R1A in alcohol consumption, and there is critical overlap in the neural pathways responsible for food consumption and those involved in excessive alcohol use (Thiele et al, 2003;Landgren et al, 2008;Landgren et al, 2010;Dickson et al, 2011;Leggio et al, 2011). Central ghrelin signaling mediates ethanol intake by activating GHS-R1As in the VTA, LDTg, and EWcp (Jerlhag et al, 2009;Kaur and Ryabinin, 2010).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

Cruz

Herman

Cote

et al. 2012

Neuropsychopharmacol

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The neural circuitry that processes natural rewards converges with that engaged by addictive drugs. Because of this common neurocircuitry, drugs of abuse have been able to engage the hedonic mechanisms normally associated with the processing of natural rewards. Ghrelin is an orexigenic peptide that stimulates food intake by activating GHS-R1A receptors in the hypothalamus. However, ghrelin also activates GHS-R1A receptors on extrahypothalamic targets that mediate alcohol reward. The central nucleus of the amygdala (CeA) has a critical role in regulating ethanol consumption and the response to ethanol withdrawal. We previously demonstrated that rat CeA GABAergic transmission is enhanced by acute and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to detect Ghsr mRNA in the CeA and performed electrophysiological recordings to measure ghrelin effects on GABA transmission in this brain region. Furthermore, we examined whether acute or chronic ethanol treatment would alter these electrophysiological effects. Our qRT-PCR studies show the presence of Ghsr mRNA in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further increased the ghrelin-induced enhancement of IPSP amplitude, but to a lesser extent than ethanol alone. When applied alone, ethanol significantly increased IPSP amplitude, but this effect was attenuated by the application of ghrelin. In neurons from chronic ethanol-treated (CET) animals, the magnitude of ghrelin-induced increases in IPSP amplitude was not significantly different from that in naive animals, but the ethanol-induced increase in amplitude was abolished. Superfusion of the GHS-R1A antagonists D-Lys3-GHRP-6 and JMV 3002 decreased evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. D-Lys3-GHRP-6 and JMV 3002 also blocked ghrelin-induced increases in GABAergic responses. Furthermore, D-Lys3-GHRP-6 did not affect ethanol-induced increases in IPSP amplitude. These studies implicate a potential role for the ghrelin system in regulating GABAergic transmission and a complex interaction with ethanol at CeA GABAergic synapses.

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Section: Discussionmentioning

confidence: 99%

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

Cruz

Herman

Cote

et al. 2012

Neuropsychopharmacol

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“…Emerged evidence suggests that feeding and reward behaviours share common complex neurochemical mechanisms and that these are mediated by the mesolimbic dopamine system (Rada, Mark, & Hoebel 1998;Hoebel et al 1999;Addolorato et al 2006;Jerlhag et al 2006;Abizaid et al 2011;Dickson et al 2011;Leggio et al 2011;Jerlhag et al 2011a;Edwards & Abizaid 2016). More specifically, gut-brain peptides, which have been traditionally known to regulate food intake and energy balance (Ahima & Antwi 2008), seem to play a pivotal role in mediating the reinforcing properties of alcohol and other drugs of abuse Abizaid et al 2011;Clifford et al 2012;Egecioglu, Engel, & Jerlhag 2013a;Suchankova et al 2013a;Engel & Jerlhag 2014;Vadnie et al 2014;Vallof et al 2016c).…”

Section: Introductionmentioning

confidence: 99%

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

2018

Self Cite

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Alcohol expresses its reinforcing properties by activating areas of the mesolimbic dopamine system, which consists of dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens. The findings that reward induced by food and addictive drugs involve common mechanisms raise the possibility that gut-brain hormones, which control appetite, such as amylin, could be involved in reward regulation. Amylin decreases food intake, and despite its implication in the regulation of natural rewards, tenuous evidence support amylinergic mediation of artificial rewards, such as alcohol. Therefore, the present experiments were designed to investigate the effect of salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, on various alcohol-related behaviours in rodents. We showed that acute sCT administration attenuated the established effects of alcohol on the mesolimbic dopamine system, particularly alcohol-induced locomotor stimulation and accumbal dopamine release. Using the conditioned place preference model, we demonstrated that repeated sCT administration prevented the expression of alcohol's rewarding properties and that acute sCT administration blocked the reward-dependent memory consolidation. In addition, sCT pre-treatment attenuated alcohol intake in low alcohol-consuming rats, with a more evident decrease in high alcohol consumers in the intermittent alcohol access model. Lastly, sCT did not alter peanut butter intake, blood alcohol concentration and plasma corticosterone levels in mice. Taken together, the present data support that amylin signalling is involved in the expression of alcohol reinforcement and that amylin receptor agonists could be considered for the treatment of alcohol use disorder in humans.

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“…The same research group discovered that ghrelin decreased the %OAT in the EPM and increased the ambulation time in the OF test in rats and neonatal chicks [15,16], hence ghrelin exerts opposite effects on behavioral patterns. The role of ghrelin in reward (see reviews in this issue: [17,18]) and in anxiety (see review: [19]) are well-examined research areas, but the role of obestatin in these research fields has not been clarified yet.…”

Section: Introductionmentioning

confidence: 99%

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

Lipták

Dochnal

Csabafi

et al. 2013

Regulatory Peptides

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Obestatin is a 23-amino acid gut-derived neuropeptide, encoded by the same gene with ghrelin. The goal of this study was to examine the effects of obestatin on the acute and chronic analgesic actions of morphine and on mild morphine withdrawal. Open-field (OF) and elevated plus maze (EPM) tests were used to assess mild morphine withdrawal-induced behavior changes and the heat-radiant tail-flick assay was used to investigate analgesic actions of morphine. CFLP male mice were treated twice a day with graded doses of morphine in EPM and OF experiments and once a day in tail-flick studies. Obestatin (1.5 μg/2 μl) was administrated once a day in all experiments. Furthermore, 0.2 mg/kg naloxone or saline was administered after the final injection of morphine at a dose of 20 mg/kg in EPM and OF. These behavioral parameters were monitored in the OF: the percentage of center ambulation time and distance; whereas in the EPM: the time spent in open arms and the entries into open arms compared to the total time (%OAT) and entries (%OAE). In the OF, obestatin significantly decreased the percentage of time spent in the center in mice undergoing naloxone-precipitated mild morphine withdrawal. EPM results were similar to open field, but obestatin had no significant effect on parameters mentioned above. Besides, obestatin maintained the analgesic effect of morphine 90 and 120 min after morphine injection in mice treated with morphine receiving obestatin compared to mice treated with morphine. In tolerance studies, obestatin diminished the analgesic tolerance to morphine on the 5th day. In this study we confirmed that obestatin reversed the effect of mild morphine withdrawal and enhances the analgesic effect of morphine. These data suggest that obestatin may have a role in opioid-induced analgesia and in behavioral responses induced by opioid withdrawal.

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

Cited by 217 publications

References 123 publications

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

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