Monoaminergic contributions to alcohol reinforcement, dependence, and relapse

Alcohol addiction is a significant public health concern; however, the neurobiological mechanisms underlying alcohol’s addictive properties are not well understood. Although classical mechanisms of alcohol action primarily involve modulation of the gamma-aminobutyric acid (GABA) ergic and opioid systems, evidence suggests that monoaminergic neurotransmission plays a critical and multifaceted role in alcohol reinforcement, reward, and dependence. This review summarizes the scientific literature on the contribution of monoaminergic systems to the effects of alcohol and the development of addiction. To this end, classical and recent studies (54% of which were published within the last five years) were identified through searches of the PubMed, Web of Science and Scopus databases, covering publications from 1987 to 2025. We synthesize evidence demonstrating that alcohol-induced alterations in the dopaminergic system represent a canonical pathway underlying alcohol reinforcement. Beyond dopamine, we highlight emerging evidence implicating norepinephrine in withdrawal-related states, salience processing, and alcohol’s reinforcing properties, as well as the role of serotonin in modulating alcohol consumption and reward through specific receptor subtypes. These monoaminergic systems interact with the classical alcohol targets to influence the initiation, maintenance, escalation and relapse vulnerability of alcohol use. Although monoaminergic mechanisms have been extensively characterized in psychostimulant addiction, their specific contributions to alcohol-related addictive processes remain comparatively underexplored. Therefore, this review aims to integrate existing research on the involvement of monoaminergic systems in the effects of alcohol and to identify knowledge gaps. This will provide a framework for future studies and the development of novel pharmacotherapeutic strategies.