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International Archives of Addiction Research and Medicine

DOI: 10.23937/2474-3631/1510006

Alcohol Withdrawal Syndrome: The Importance of Glutamatergic System

José Carlos F. Galduróz*, Pedro Luis Prior and Anna Carolina Ramos

Department of Psychobiology, Universidade Federal de São Paulo, Brazil

*Corresponding author: Jose Carlos F. Galduroz, Department of Psychobiology, Federal University of Sao Paulo, Brazil, E-mail:
Int Arch Addict Res Med, IAARM-1-006, (Volume 1, Issue 2), Editorial; ISSN: 2474-3631
Received: July 22, 2015 | Accepted: July 27, 2015 | Published: July 30, 2015
Citation: Galduróz JCF, Prior PL, Ramos AC (2015) Alcohol Withdrawal Syndrome: The Importance of Glutamatergic System. Int Arch Addict Res Med 1:006e. 10.23937/2474-3631/1510006
Copyright: © 2015 Galduróz JCF. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Alcohol withdrawal syndrome (AWS) is a complex phenomenon that involves several neurotransmission systems. Its signs and symptoms are related to the adrenergic autonomic hyperstimulation and to the hypofunction of the gabaergic system. Moreover, alcohol is an antagonist of the NMDA (N-Methyl-D-Aspartate) receptors, which are excitatory, in the central nervous system [1].

The glutamatergic hyperactivity resulting from AWS via NMDA receptors would cause a large calcium influx, and increase the activity of the nitric oxide synthase enzyme.This action would increase the excitotoxic activity, accelerate the production of oxygen free radicals and cause neuronal death [2].

It is known that the glutamatergic hyperactivity results in great damage to the cortical function; concentration and impulse control [3-6]. Impulsivity and damage to frontal functions are considered risk factors for the development of alcohol dependence [7,8], and AWS would aggravate such damage, thus contributing to the perpetuation of this dependence [9,10].

Several studies have shown the association between the number of previous AWS episodes and cognitive deficits [11,12] caused by neurodegeneration of pre-frontal areas [13], in turn caused by glutamatergic hyperfunction [14]. Czapla et al. (2015) [15] have concluded that the number of AWS episodes is a significant predictor of relapse and decreased impulse control by individuals with alcohol dependence.

These phenomena are perfect examples of the vicious cycle the addicted brain may enter when in abstinence of any psychotropic substance. Even though permanent use of alcohol may damage neurons, sudden lack of this substance in the brain is toxic in much the same way, stimulating oxidative processes in the central nervous system, leading to neuron death and neuron lesions, which, in turn, may result in aggravating symptoms in the long run.

In order to prevent this perpetuating cycle, one of the main measures clinicians should implement is the adequate treatment of AWS as a clinical condition of great significance that should be treated with pharmacological, behavioral and social approaches.

Even though there are many pharmacological studies concerning the treatment of AWS, there is still the need to find new substances that modulate the glutamatergic system [16]. We have recently proposed the use of microelements such as zinc and magnesium as such substances, as they are natural modulators of this system. In fact, in a study we developed, we observed a direct association between lower plasmatic levels of zinc and magnesium and greater intensity of AWS symptoms [17].

Therefore, it stresses the importance of early identification and implementation of effective measures to treat and attenuate the AWS as well as focus on relapse prevention [18,19].

  1. Matsumoto I (1998) Molecular neurobiology of alcohol withdrawal. J Neurochem 70: 45.

  2. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59: 1609-1623.

  3. Jung ME, D. B. Metzger (2010) Alcohol Withdrawal and Brain Injuries: Beyond Classical Mechanisms. Molecules 15: 4984-5011

  4. Li-Smerin Y, Levitan ES, Johnson JW (2001) Free intracellular Mg(2+) concentration and inhibition of NMDA responses in cultured rat neurons. J Physiol 15: 729-743.

  5. George O, Sanders C, Freiling J, Grigoryan E, Vu S, et al. (2012) Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking. ProcNatlAcadSci USA 109: 18156-18161.

  6. Bisaga A, Popik P, Bespalov AY, Danysz W (2000) Therapeutic potential of NMDA receptor antagonists in the treatment of alcohol and substance use disorders. Expert OpinInvestig Drugs 9: 2233-2248.

  7. Littleton J (1998) Neurochemical mechanisms underlying alcohol withdrawal. Alcohol Health Res World 22: 13-24.

  8. Smith JL, Mattick RP, Jamadar SD, Iredale JM (2014) Deficits in behavioural inhibition in substance abuse and addiction: A meta-analysis. Drug Alcohol Depend 145:1-33.

  9. Crews FT, Boettiger CA (2009) Impulsivity, frontal lobes and risk for addiction. PharmacolBiochemBehav 93: 237-247.

  10. Rubio G M, Jimenez R, Rodriguez-Jimenez I, Martinez C, AvilaF, et al. (2008) The role of behavioral impulsivity in the development of alcohol dependence: a 4-year follow-up study. AlcoholClinExp Res 32: 1681-1687.

  11. Loeber S, Duka T, Welzel H, Nakovics H, Heinz A, et al. (2009) Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications. Alcohol Alcohol 44: 372-381.

  12. Loeber S, Duka T, Welzel-Márquez H, Nakovics H, Heinz A, et al. (2010) Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse. Alcohol Alcohol 45: 541-547.

  13. Duka T, Stephens DN (2014) Repeated detoxification of alcohol-dependent patients impairs brain mechanisms of behavioural control important in resisting relapse. Curr Addict Rep 1: 1-9.

  14. Crews FT, Nixon K (2009) Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol 44: 115-127

  15. Czapla M, Simon JJ, Richter B, Kluge M, Friederich HC, et al. (2015) The impact of cognitive impairment and impulsivity on relapse of alcohol-dependent patients: implications for psychotherapeutic treatment. Addict Biol.

  16. Prior PL, Galduróz JCF (2011) Glutamatergic hyperfunctioning during alcohol withdrawal syndrome: therapeutic perspective with zinc and magnesium. Med Hypotheses 77: 368-370.

  17. Prior PL, Vaz MJ, Ramos AC, Galduróz JCF (2015) Influence of microelement concentration on the intensity of alcohol withdrawal syndrome. AlcoholAlcohol 50: 152-156.

  18. Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, et al. (2015) Identification and Management of Alcohol Withdrawal Syndrome. Drugs 75: 353-365

  19. Melson J, Kane M, Mooney R, Mcwilliams J, Horton T (2014) Improving alcohol withdrawal outcomes in acute care. Perm J 18: 141-145.

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