Low-level developmental lead exposure increases risk of relapse to alcohol seeking in mice

A new IU study examining effects of low-level developmental lead exposure in mice could explain why some people dependent on alcohol return to using.

The study, published in Neuropharmacology, looked at whether developmental lead exposure can increase the propensity to relapse to alcohol consumption in mice. The researchers also looked at the effects on the expression of synaptic and non-synaptic glutamate transporters -- regulators of brain motivation and reinforcing circuits-- in brain regions associated with drug addiction.

Our data in mice suggests that early life, low-level lead exposure does not lead to the development of an alcohol use disorder in adults per see. However, it does alter brain circuits in such a way that once a dependency is developed, it makes it harder to refrain from turning back to alcohol."

Stephen Boehm, Professor, Department of Psychology, IUPUI

Although there have been efforts to reduce environmental exposure to lead and to prevent lead poisoning, Boehm said exposure still exists and can cause serious harm and significant health problems, even at low levels. Studies of adults with a history of childhood lead exposure have consistently demonstrated cognitive impairments associated with sustained glutamate signaling.

Boehm and his team studied whether developmental lead exposure increased motivation to consume alcohol by testing mice in an alcohol self-administration paradigm.

The study suggests that low-level lead exposure for humans during childhood and adolescence - so low that kids growing up in old industrial cities might be exposed by merely kicking up dirt during normal play - may be sufficient to enhance relapse to alcohol use in adults struggling with alcohol use disorder.

Their study also suggests that reduced expression of proteins responsible for taking up the neurotransmitter glutamate in dorsolateral striatum - a brain region believed to be involved in the development of compulsive drug taking - may be associated with this effect. Glutamate is a key player in the executive control of dorsolateral striatal function. So, dysfunction in glutamate signaling may well have implications for the development of compulsive drinking (characteristic of individuals with alcohol use disorder).

Boehm said future work is needed, but the current project demonstrates the need for additional policies around environmental lead exposure.

"This study not only gives us further insight into addiction and the brain, but it might also lead to a call for changes in policies around lead exposure that could help keep our children safe."

Corresponding authors include Claudia Rangel-Barajas, Israel Coronel, Yanping Zhang and Maribel Hernandez, from the School of Science at IUPUI.

Responding to the Addictions Crisis

The Responding to the Addictions Crisis Grand Challenge initiative engages a broad array of IU's world-class faculty, as well as IU's business, nonprofit and government partners. Working together, the groups are contributing to an initiative to implement a comprehensive plan to reduce deaths from addiction, ease the burden of drug addiction on Hoosier communities and improve health and economic outcomes. This initiative is one of the nation's largest and most comprehensive state-based responses to the opioid addiction crisis -- and the largest led by a university.

Journal reference:

Rangel-Barajas, C., et al. (2020) Low-level developmental lead exposure does not predispose to adult alcohol self-administration, but does increase the risk of relapsing to alcohol seeking in mice: Contrasting role of GLT1 and xCT brain expression. Neuropharmacology. doi.org/10.1016/j.neuropharm.2020.108339.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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