Journal
ADDICTION BIOLOGY
Volume 26, Issue 2, Pages -Publisher
WILEY
DOI: 10.1111/adb.12936
Keywords
AMPK; drug addiction; energy sensors; mTOR; reward brain circuitry
Categories
Funding
- RETICS Red de Trastornos Adictivos
- Instituto de Salud Carlos III (ISCIII)
- Ministerio de Economia y Competitividad (MINECO)
- European Regional Development Funds-European Union (ERDF-EU) [RD16/0017/0001]
- ISCIII
- MINECO
- ERDF-EU [PI19/00343, PI19/01577, IFI18/00042]
- Ministerio de Sanidad, Servicios Sociales e Igualdad, and Plan Nacional sobre Drogas [PND2019/040, PND2018/044]
- National System of Health
- FIMABIS [CPII17/00024]
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Addiction involves repeated exposure and compulsive seeking of psychotropic drugs, leading to relapse despite harmful effects. Neuroadaptation mechanisms in reward circuits result in changes in neurotransmission and cellular structure, impacting neuronal energy balance and protein synthesis. Targeting metabolic sensors like AMPK and mTOR could lead to novel pharmacotherapies for individualized treatment of drug abuse.
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 K(ATP)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.
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