Logo image
Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research
Journal article   Peer reviewed

Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research

Catherine A Marcinkiewcz, Emily G Lowery-Gionta and Thomas L Kash
Alcoholism, clinical and experimental research, Vol.40(6), pp.1192-1201
06/2016
DOI: 10.1111/acer.13076
PMID: 27161942

View Online

Abstract

Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs. Given the heterogeneity in responsiveness to serotonergic drugs across the spectrum of alcoholic subtypes, we assess the contribution of specific 5-HT circuits to discrete endophenotypes of alcohol dependence. 5-HT circuits play a distinctive role in reward, stress, and executive function which may account for the variation in response to serotonergic drugs. New optogenetic and chemogenetic methods for dissecting 5-HT circuits in alcohol dependence may provide clues leading to more effective pharmacotherapies. Although our current understanding of the role of 5-HT systems in alcohol dependence is incomplete, there is some evidence to suggest that 5-HT3 receptor antagonists are effective in people with the L/L genotype of the 5-HTTLPR polymorphism while SSRIs may be more beneficial to people with the S/L or S/S genotype. Studies that assess the impact of serotonin transporter polymorphisms on 5-HT circuit function and the subsequent development of alcohol use disorders will be an important step forward in treating alcohol dependence.
Serotonin - physiology Endophenotypes Humans Serotonin Uptake Inhibitors - therapeutic use Serotonin Uptake Inhibitors - adverse effects Substance Withdrawal Syndrome - drug therapy Substance Withdrawal Syndrome - complications Anxiety - drug therapy Polymorphism, Genetic Serotonin 5-HT3 Receptor Antagonists - therapeutic use Depression - drug therapy Serotonin Plasma Membrane Transport Proteins - genetics Animals Anxiety - complications Alcoholism - genetics Depression - complications Alcoholism - complications Alcoholism - drug therapy Alcoholism - physiopathology

Details

Logo image