Orexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence

Carvajal, Francisca; Alcaraz-Iborra, Manuel; Lerma-Cabrera, José Manuel; Valor, Luis M.; Fuente, Leticia de la; Sanchez-Amate, Maria del Carmen; Cubero, Inmaculada

doi:10.1016/j.bbr.2015.03.046

Cited by 20 publications

(21 citation statements)

References 65 publications

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“…Because rodents are nocturnally active, the drinking-in-the-dark (DID) model is used to examine binge-like ethanol consumption during periods of darkness. [33][34][35] EtOH conditioning in the dark chamber leads to arousal effects in mice and influences the rewarding effects of EtOH, as seen in the present study.…”

Section: Discussionsupporting

confidence: 56%

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

Shimizu

Oki

Mitani

et al. 2015

Biological & Pharmaceutical Bulletin

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The rewarding effects of alcohol can lead to progressively heavier and more frequent drinking. Since studies of reward have mainly focused on responses to higher alcohol doses, the relations between reward and moderate/sustained alcohol exposure remain unknown. Our objective was to evaluate factors affecting the reward value of low alcohol doses and risk factors for increasing alcohol doses due to reward progression caused by alcohol exposure patterns. We thus performed conditioned place preference (CPP) and ethanol (EtOH)-induced locomotor sensitization tests in mice. Low-dose EtOH (0.5 or 1 g/kg twice/week)-induced CPP was stronger than that produced by saline control treatment, but the effect decreased with increasing numbers of conditioning trials. Moderate-dose/long-term EtOH exposure induced a weaker CPP than high-dose/short-term EtOH (2 g/kg twice/week) exposure with the same total EtOH dose (8 g/kg/experiment). Acamprosate calcium, an anti-relapse drug, preclusively reduced EtOH-induced CPP. EtOH induced CPP and locomotor sensitization in black but not white chamber, although the initial preference and the basal locomotion in each chamber were equal. Therefore the brightness of the chamber had an effect on EtOHinduced sensitization. Moreover, additional studies indicated that EtOH-induced locomotor sensitization also depends on the dose but not the administration interval. Paired associative learning with EtOH exposure is a potent factor influencing the level of reward produced by EtOH. Moreover, exposure to high doses of alcohol, even on an intermittent schedule, carries a higher risk of addiction than exposure to moderate doses over longer periods.Key words moderate alcohol (ethanol: EtOH); conditioned place preference (CPP); reward; sensitization; paired associative learning Alcohol abuse is associated with serious physical and psychiatric illnesses, financial hardships, familial dysfunction, and violence, all of which place a substantial burden on society. Heavy alcohol consumption and long-term drinking increase the risk of alcohol-related diseases such as liver cirrhosis, cancer, pancreatitis, and depression. 1,2) In response, the World Health Organization (WHO) recently approved a Global Strategy to Reduce Harmful Use of Alcohol urging all countries to strengthen national responses to public health problems caused by alcohol use.3) In Japan, 6.45 million people suffer from alcohol-related problems, with an estimated annual economic loss of 4.15 trillion yen associated with alcohol. 4) In December 2013, the Basic Act on Measures against Alcohol-related Health Harm was enacted in Japan, promoting education about drinking in moderation to prevent alcoholrelated problems.Regular consumption of alcohol increases the propensity for addiction because of the rewarding effects of alcohol. Thus, many casual drinkers gradually increase total alcohol consumption, which becomes habitual over time. Although many studies in rodents have been conducted on chronic drinking and reward, 5-7) previous studies have ma...

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Section: Discussionsupporting

confidence: 56%

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

Shimizu

Oki

Mitani

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Also utilizing the DID paradigm, another study examined lower doses of the OX 1 antagonist SB-334867 (5, 10 mg/kg, i.p.) in C57BL/6J mice [29]. A dose-related reduction was observed in the first hour of alcohol consumption, but no reduction was seen 2 h after administration relative to controls.…”

Section: Peripheral and Central Ox Receptor Targetingmentioning

confidence: 83%

“…This increase in OX mRNA may be produced in response to OX release [27]. In the LH, four daily DID sessions of saccharin, but not alcohol, reduced OX 1 receptor mRNA expression of C57BL/6J mice [29]. The authors hypothesized that receptor down regulation may act as a protective mechanism, preventing escalating overconsumption, as observed with saccharin consumption.…”

Section: Role Of Alcohol In Orexin System Expression/activationmentioning

confidence: 99%

“…Central administration of SB-334867 (3 μg/μL, i.c.v.) has also been assessed in the DID paradigm [29]. This dose attenuated alcohol consumption and corresponding BECs but not 0.15 % saccharin or food consumption, suggesting that the discrepancies seen by Olney et al [27] may be due to procedural differences, peripheral interactions or dosage effects.…”

Section: Peripheral and Central Ox Receptor Targetingmentioning

confidence: 99%

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Role of Lateral Hypothalamic Orexin (Hypocretin) Neurons in Alcohol Use and Abuse: Recent Advances

Ch’ng

Lawrence

2016

Curr Pharmacol Rep

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Purpose of Review Alcohol use disorders (AUDs) are chronic relapsing disorders with the modest efficacy of current medications. The US Food and Drug Administration (FDA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) approval of the dual orexin (OX) receptor antagonist, suvorexant for the treatment of insomnia, may enable repurposing of this drug for the treatment of other diseases. Here, we summarize and reflect on the most recent research on the role of OX neurons in alcohol use and abuse. Recent Findings OX neurons regulate alcohol intake and seeking, although their involvement in different aspects of alcohol consumption/seeking, specific loci of action and interactions with other transmitter systems are still being clarified. Summary Recent studies have identified anatomic loci of action and interactions between OX and other neuropeptides that drive alcohol seeking. Future studies are required to fully elucidate these behaviors, in which optogenetic and chemogenetic approaches may prove useful.

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“…Third, recent studies have highlighted the role of OX system in binge-like consumption of rewarding stimulus (sucrose, saccharin and ethanol) in non-dependent animals (Alcaraz-Iborra et al, 2014;Anderson et al, 2014;Olney et al, 2015) as measured by the Drinking in the Dark (DID) paradigm, a wellestablished procedure to reproduce pre-dependent episodes of human binge consumption patterns in mice (Thiele and Navarro, 2014). Thus, the OXr1 antagonist SB-334867 reduced sucrose, saccharin (AlcarazIborra et al, 2014) and ethanol (Anderson et al, 2014;Olney et al, 2015) binge-like drinking when administered peripherally and ethanol binge-like drinking when centrally infused (Carvajal et al, 2015) in non-deprived mice. Moreover, additional to pharmacological studies, in our lab we observed that following 4 repetitive episodes of bingelike consumption of both sucrose and saccharin, OX mRNA expression was dampened in the lateral hypothalamus (LH), suggesting a shortterm adaptive and compensatory reduction of OX synthesis in response to binge-like consumption (Alcaraz-Iborra et al, 2014).…”

Section: Oxr1 Signaling Modulates Impulsivity and Binge-like Consumptmentioning

confidence: 96%

Do Orexins contribute to impulsivity-driven binge consumption of rewarding stimulus and transition to drug/food dependence?

Alcaraz-Iborra

Cubero

2015

Pharmacology Biochemistry and Behavior

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Orexin receptor 1 signaling contributes to ethanol binge-like drinking: Pharmacological and molecular evidence

Cited by 20 publications

References 65 publications

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice

Role of Lateral Hypothalamic Orexin (Hypocretin) Neurons in Alcohol Use and Abuse: Recent Advances

Do Orexins contribute to impulsivity-driven binge consumption of rewarding stimulus and transition to drug/food dependence?

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