Substance Abuse Beyond Dopamine and Impulsivity

Summary: Researchers shed new light on why some individuals are more vulnerable to substance abuse than others, focusing on the relationship between impulsivity, dopamine production, and cocaine use. Through a study on rats, they discovered that impulsivity predicts cocaine consumption not through dopamine production capacity but possibly through the control of its release.

This groundbreaking work challenges the conventional belief that regular cocaine use diminishes the brain’s ability to produce dopamine, suggesting that the mechanisms of vulnerability to drug abuse are more complex than previously thought.

Key Facts:

  1. Impulsive action, rather than risky decision-making, is a better predictor of increased cocaine use, indicating a specific aspect of impulsivity influences drug abuse vulnerability.
  2. Contrary to previous assumptions, chronic cocaine consumption does not affect the brain’s capacity to produce dopamine, debunking the idea that reduced dopamine synthesis is a consequence of regular drug use.
  3. The study suggests that individual differences in drug abuse vulnerability may stem from variations in how dopamine release is controlled, rather than the capacity for dopamine production.

Source: University of Geneva

Why do some people who try drugs struggle with substance abuse while others don’t? This question has long puzzled scientists.

A team from the University of Geneva (UNIGE) explored the complex interplay between personality traits and brain chemistry. The scientists studied the role of impulsivity and the production of dopamine – the so-called ‘‘happiness hormone’’ – in influencing the risk of cocaine abuse.

These results, published in eNeuro, offer new keys to understanding vulnerability to drug abuse, which could lead to the development of more targeted interventions for people at risk.

This shows a woman and pills.
These results suggest dopamine synthesis is probably not the main driver of impulsivity or vulnerability to cocaine use. Credit: Neuroscience News

When a person consumes an addictive drug, his or her dopamine release surges, creating a “high” feeling. With repeated drug use, this dopamine release drops, potentially driving the person to increase drug consumption. This mechanism varies between individuals, with some showing a greater propensity to consume the drug while others don’t. However, the reasons for these differences are unknown.

Cocaine does not affect dopamine production capacity

In a recent study, a UNIGE team explored the complex interaction between different impulsive behaviors, the production of dopamine and the use of drugs, more specifically cocaine. Does an impulsive personality increase the vulnerability to drug abuse? Does an impulsive individual produce more or less dopamine?

To find out, the scientists studied two groups of rats, one made up highly impulsive individuals, the other of less impulsive ones. These animals were trained to self-administer cocaine at a dose that triggers dopamine neuroadaptations without harming their health.

Scientists first trained the animals in a gambling task to measure two impulsive behaviors: impulsive action – the inability to control automatic actions – and risky decision-making – the acceptance of more risk when making decisions.

Scientists then measured the level of dopamine synthesis using a non-invasive neuroimaging technique before and after cocaine intake in the two groups of rats. They found that impulsive action, but not risky decision-making, predicted a greater number of cocaine injections and faster cocaine use.

“However, we observed that there was no difference in the capacity to produce dopamine between the highly impulsive and less impulsive animals. In other words, impulsivity and vulnerability to cocaine abuse might not be linked to dopamine production, but to mechanisms controlling its release,’’ explains Ginna Paola Urueña-Méndez, PhD. student in the Department of Psychiatry and the Department of Basic Neurosciences in the Faculty of Medicine at the UNIGE, and first author of the study.The team then assessed repeated cocaine use and its impact on dopamine levels in the two groups of rodents.

‘‘Until now, the idea that regular cocaine consumption could reduce the ability to produce dopamine was accepted. Our results contradict this assumption as both populations of rats retained the same capacity to produce dopamine, despite chronic consumption,’’ explains Nathalie Ginovart, Associate Professor in the Department of Psychiatry and the Department of Basic Neurosciences at the UNIGE Faculty of Medicine, who led this research.

Identifying other mechanisms

These results suggest dopamine synthesis is probably not the main driver of impulsivity or vulnerability to cocaine use. They also contradict the hypothesis that cocaine use may directly reduce the capacity to produce dopamine.

This work represents a significant advance in research into the risk of drug abuse. It opens the door to exploring other mechanisms that could explain individual vulnerability to drugs.

‘‘This variation in vulnerability could be linked to differences in the relative reactivity of dopaminergic neurons, so that certain stimuli, including drugs, are more salient for more impulsive animals,’’ say the researchers. The team is currently continuing its research to assess how mechanisms controlling dopamine neuron reactivity influence vulnerability to abuse drugs.

About this addiction and neuroscience research news

Author: Antoine Guenot
Source: University of Geneva
Contact: Antoine Guenot – University of Geneva
Image: The image is credited to Neuroscience News

Original Research: Open access.
Decoupling Dopamine Synthesis from Impulsive Action, Risk-Related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [18F]-FDOPA PET Study in Roman High- and Low-Avoidance Rats” by Ginna Paola Urueña-Méndez et al. eNeuro


Decoupling Dopamine Synthesis from Impulsive Action, Risk-Related Decision-Making, and Propensity to Cocaine Intake: A Longitudinal [18F]-FDOPA PET Study in Roman High- and Low-Avoidance Rats

Impulsive action and risk-related decision-making (RDM) are two facets of impulsivity linked to a hyperdopaminergic release in the striatum and an increased propensity to cocaine intake.

We previously showed that with repeated cocaine exposure, this initial hyperdopaminergic release is blunted in impulsive animals, potentially signaling drug-induced tolerance.

Whether such dopaminergic dynamics involve changes in dopamine (DA) synthesis as a function of impulsivity is currently unknown.

Here, we investigated the predictive value of DA synthesis for impulsive action, RDM, and the propensity to take cocaine in a rat model of vulnerability to cocaine abuse. Additionally, we assessed the effects of cocaine intake on these variables.

Rats were tested sequentially in the rat Gambling Task (rGT) and were scanned with positron emission tomography and [18F]-FDOPA to respectively assess both impulsivity facets and striatal DA synthesis before and after cocaine self-administration (SA).

Our results revealed that baseline striatal levels of DA synthesis did not significantly predict impulsive action, RDM, or a greater propensity to cocaine SA in impulsive animals.

Besides, we showed that impulsive action, but not RDM, predicted higher rates of cocaine taking. However, chronic cocaine exposure had no impact on DA synthesis, nor affected impulsive action and RDM.

These findings indicate that the hyper-responsive DA system associated with impulsivity and a propensity for cocaine consumption, along with the reduction in this hyper-responsive DA state in impulsive animals with a history of cocaine use, might not be mediated by dynamic changes in DA synthesis.

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