Project: Studying the role of environmental pollutants in vulnerability to addiction in animal models.
Related objective: To study whether environmental pollutants can facilitate the incidence of addictive behaviors in laboratory animals.
Overview: Addiction is currently recognized as a neurobiological disease where the repeated abuse of psychoactive substances disrupts the normal reward circuitry. Psychoactive substances are all those chemical substances that can alter mood, sleep/wake cycles, activity levels, etc. Environmental factors such as acute or chronic stress affect this dopaminergic reward system and increase the risk of psychoactive substance use and relapse. Several studies support the idea that exposure to environmental pollution can contribute to cognitive and psychiatric disorders; some associate exposure to environmental pollution with substance abuse. Similarly, pesticide use in agriculture is linked to several central nervous system disorders associated with dopaminergic neurotransmission, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD). Dopamine (DA) is the critical neurotransmitter in the reward circuit that mediates substance abuse; thus, exposure to certain environmental neurotoxins could influence the development of drug addiction. For decades, our Laboratory studied the neurotoxic effects of the herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) in animal models. It was the first to demonstrate that chronic exposure to 2,4-D induced behavioral and neurochemical changes associated with alterations in dopaminergic neurotransmission. For some years now, it has also been studying the long-term effects of cocaine in an animal model that allows us to identify the neuroadaptations underlying the behavioral changes observed in addiction, enabling us to link behavioral changes with molecular ones. It was the first to describe the involvement of the Wnt/β-catenin signaling pathway in long-term neuroadaptations induced by cocaine and stress. This suggests that this signaling pathway plays an important role in vulnerability to the effects of drugs. This evidence has led us to study the impact of environmental pollutants, especially the herbicide 2,4-D, widely used in our country, on vulnerability to developing addiction. To this end, we will use a model that allows us to identify cocaine-induced neuroadaptations in rats previously exposed to environmental pollutants through their food. This will enable us to evaluate: 1) whether exposure to environmental pollutants during the evaluated periods produces an increased response to cocaine, known as sensitization; 2) whether environmental pollutants produce alterations in dopaminergic neurotransmission in brain areas involved in addiction; 3) whether effectors of the Wnt signaling pathways are involved in this increased vulnerability; and 4) whether exposure to environmental pollutants induces behavioral changes.
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Director: Cintia N. Konjuh
Members: Alejandra M. Pacchioni, Alejandrina Funes, Abraham Ramírez, Lucía Trossero.
Spaces/Institutions/Academic Units: Faculty of Biochemical and Pharmaceutical Sciences (UNR)
Contact
ckonjuh@fbioyf.unr.edu.ar