The role of the opioid system in alcohol dependence

Abstract

The role of the brain opioid system in alcohol dependence has been the subject of much research for over 25 years. This review explores the evidence: firstly describing the opioid receptors in terms of their individual subtypes, neuroanatomy, neurophysiology and ligands; secondly, summarising emerging data from specific neurochemical, behavioural and neuroimaging studies, explaining the characteristics of addiction with a focus on alcohol dependence and connecting the opioid system with alcohol dependence; and finally reviewing the known literature regarding opioid antagonists in clinical use for alcohol dependence. Further interrogation of how modulation of the opioid system, via use of MOP (mu), DOP (delta) and KOP (kappa) agents, restores the balance of a dysregulated system in alcohol dependence should increase our insight into this disease process and therefore guide better methods for understanding and treating alcohol dependence in the future.

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

“…Research regarding KORs and alcohol addiction has become more prevalent in the last decade, with a greater emphasis being placed on the molecular role of the dynorphin system (Faisal et al 2014) and its potential therapeutic role in alcoholism (Heilig & Schank 2014, Nutt 2014, Walker et al 2012). Leeman et al discussed in depth how various animal models can appropriately recapitulate human studies, and importantly, the authors highlight the role alcohol consumption and abstinence (as well as heavy drinking) can play in informing the human literature (Leeman et al 2010).…”

Decreased [³H]naloxone Binding in the Dentate Gyrus of Cloninger Type 1 Anxiety-Prone Alcoholics: A Postmortem Whole-Hemisphere Autoradiography Study

“…Three "classical" opioid receptors include the mu-opioid, the delta-opioid, and kappa-opioid receptors (MOR, DOR, and KOR, respectively) (Nutt, 2013). MOR is the major receptor target of abused opioids (Bond et al, 1998), and also a target of nonopioid drugs of abuse, such as ethanol (EtOH) (Herz, 1997).…”

“…MOR is the major receptor target of abused opioids (Bond et al, 1998), and also a target of nonopioid drugs of abuse, such as ethanol (EtOH) (Herz, 1997). The interactions between MOR and alcohol have been widely studied (Nutt, 2013). A critical function of the CNS opioidergic system, as it relates to addiction, is the inhibition of the GABAergic neurons of the ventral tegmental area (VTA) by the activation of MORs.…”

“…The MOR distribution in the CNS has been thoroughly studied in rodents, and according to rodent autoradiographic studies, MORs can be found throughout the CNS and especially in brain areas that are essential to addiction and reward, for example, Nac, prefrontal cortex, caudate, putamen, and hippocampus (Nutt, 2013). Several rodent studies suggest that there are innate differences in MOR binding between preferring and nonpreferring animals in brain areas that are essential for addiction, reward, and learning, although some results seem contradictory.…”

Clinical Relevance of As-Needed Treatment with Nalmefene in Alcohol-Dependent Patients

“…Nalmefene is an opioid system modulator, with antagonist activity at the μ- and δ-receptors and partial agonist activity at the κ-receptor [1,2,3,4]. It was recently granted market authorisation in the European Union as the first pharmacological therapy approved for the reduction of alcohol consumption in adult patients with alcohol dependence that have a high drinking risk level according to the World Health Organisation [5] (men: >60 g/day and women: >40 g/day) and who continue to have that 2 weeks after initial assessment [6].…”