Energy production failure in human drug addiction


Drug addiction is a neuropsychiatric disorder characterized by a set of cognitive, behavioural and physiological symptoms caused by a continuous consumption of the substance, despite the harmful consequences.

Repeated exposure to drugs of abuse induce exaggerated dopamine neuronal release in ventral tegmental area, leading to fast, large and short-lasting increases of its concentration in nucleus accumbens, resulting in a reinforcement and addiction state. The mechanisms of action for different drug types influence the nature of the molecular and cellular changes produced; furthermore, these alterations have been associated with bioenergetics’ dysfunction.

The aim of the present study, comprising 30 addicted individuals and 56 controls, is to perform the analysis of the effects of prolonged drug abuse in the mitochondrial respiratory chain activity (MRC) of lymphocytes derived from blood and in the ATP plasma levels. The blood samples were collected when patients arrived at the clinical unit to begin the detoxification treatment.

The methods used include the double wavelength spectrophotometric analysis of enzymatic activity of the MRC complexes, normalized to citrate synthase (Grazina, 2012) and the luminometry assay for the quantification of plasma ATP content (Gorman et al., 2003).

The results revealed statistically significant decrease for complexes II, III, IV, II+III, I+III and GPCCR enzymatic activities in patients, compared to controls. The substances preferentially consumed like Heroin or Methadone, Buprenorphine and Suboxone (used without therapeutic purpose) were the drugs with higher impact in MRC activity, followed by alcohol and others (cocaine and cocaine+heroin), demonstrating that the continued use of drugs induce severe MRC deficiency, compromising cellular energetic efficiency.

The plasma ATP concentration is similar for patients and control group, suggesting that purinergic receptors may be involved in addiction and there are additional mechanisms interfering with ATP concentration, besides oxidative phosphorylation.

In conclusion, the present work is a relevant contribution for a better understanding of the bioenergetics’ compromise in drug addiction, particularly in human samples research.


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