Energy sensors in drug addiction: A potential therapeutic target.

Abstract

Addiction is defined as the repeated exposure and compulsive seek of psychotropic drugs that, despite the harmful effects, generate relapse after the abstinence period. The psychophysiological processes associated with drug addiction (acquisition/expression, withdrawal, and relapse) imply important alterations in neurotransmission and changes in presynaptic and postsynaptic plasticity and cellular structure (neuroadaptations) in neurons of the reward circuits (dopaminergic neuronal activity) and other corticolimbic regions. These neuroadaptation mechanisms imply important changes in neuronal energy balance and protein synthesis machinery. Scientific literature links drug-induced stimulation of dopaminergic and glutamatergic pathways along with presence of neurotrophic factors with alterations in synaptic plasticity and membrane excitability driven by metabolic sensors. Here, we provide current knowledge of the role of molecular targets that constitute true metabolic/energy sensors such as AMPK, mTOR, ERK, or KATP in the development of the different phases of addiction standing out the main brain regions (ventral tegmental area, nucleus accumbens, hippocampus, and amygdala) constituting the hubs in the development of addiction. Because the available treatments show very limited effectiveness, evaluating the drug efficacy of AMPK and mTOR specific modulators opens up the possibility of testing novel pharmacotherapies for an individualized approach in drug abuse.

• Authors: Antonio Jesús López-Gambero, Fernando Rodríguez de Fonseca, Juan Suárez
• Journal: Addiction biology (Addict Biol) Vol. 26 Issue 2 Pg. e12936 (03 2021) ISSN: 1369-1600 [Electronic] United States
• PMID: 32638485 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2020 Society for the Study of Addiction.

Chemical References

• G Protein-Coupled Inwardly-Rectifying Potassium Channels
• Glutamic Acid
• gamma-Aminobutyric Acid
• TOR Serine-Threonine Kinases
• Mitogen-Activated Protein Kinases
• AMP-Activated Protein Kinases
• Dopamine

Topics

• AMP-Activated Protein Kinases (metabolism)
• Brain (pathology)
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects)
• G Protein-Coupled Inwardly-Rectifying Potassium Channels (metabolism)
• Glutamic Acid (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Motivation
• Neuronal Plasticity (physiology)
• Reward
• Sociodemographic Factors
• Substance-Related Disorders (pathology)
• TOR Serine-Threonine Kinases (metabolism)
• gamma-Aminobutyric Acid (metabolism)