Energy sensors in drug addiction: A potential therapeutic target
Addiction Biology. 2020-07-07; 26(2):
DOI: 10.1111/adb.12936
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López-Gambero AJ(1), Rodríguez de Fonseca F(2), Suárez J(2).
Author information:
(1)Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional
Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
(2)Instituto de Investigación Biomédica de Málaga (IBIMA), UGC Salud Mental,
Hospital Regional Universitario de Málaga, Málaga, Spain.
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.
© 2020 Society for the Study of Addiction.