Abstract
Disturbances caused by excess or shortages of certain elements can affect the cerebral reward system and may therefore modulate the processes associated with the development of dependence as was confirmed by behavioural studies on animals addicted to morphine. Earlier publications demonstrated and proved the neurodegenerative properties of both low and high doses of fluoride ions in animal experiments and in epidemiological and clinical studies. The aim of the experiments conducted in the course of the present study was to analyse the effect of pre- and postnatal exposure to 50 ppm F− on the initiation/development of morphine dependence. For this purpose, the following were conducted: behavioural studies, the analysis of concentrations of dopamine and its metabolites, and the analyses of mRNA expression and dopamine receptor proteins D1 and D2 in the prefrontal cortex, striatum, hippocampus, and cerebellum of rats. In this study, it was observed for the first time that pre- and postnatal exposure to fluoride ions influenced the phenomenon of morphine dependence in a model expressing withdrawal symptoms. Behavioural, molecular, and neurochemical studies demonstrated that the degenerative changes caused by toxic activity of fluoride ions during the developmental period of the nervous system may impair the functioning of the dopaminergic pathway due to changes in dopamine concentration and in dopamine receptors. Moreover, the dopaminergic disturbances within the striatum and the cerebellum played a predominant role as both alterations of dopamine metabolism and profound alterations in striatal D1 and D2 receptors were discovered in these structures. The present study provides a new insight into a global problem showing direct associations between environmental factors and addictive disorders.
Highlights
Fluoride is a neurotoxic ion both in vitro and in vivo [1,2,3]
Disturbances caused by excess or shortages of certain elements can affect the cerebral reward system and may modulate the processes associated with the development of dependence as was confirmed by behavioural studies on animals addicted to morphine
The following were conducted: behavioural studies, the analysis of concentrations of dopamine and its metabolites, and the analyses of mRNA expression and dopamine receptor proteins D1 and D2 in the prefrontal cortex, striatum, hippocampus, and cerebellum of rats. It was observed for the first time that pre- and postnatal exposure to fluoride ions influenced the phenomenon of morphine dependence in a model expressing withdrawal symptoms
Summary
Chronic fluoride exposure has a negative impact on brain function, leading to neuronal apoptosis [4] It leads to generation of free radicals, increases lipid peroxidation in the brain, and inhibits the production of antioxidant enzymes, resulting in the formation of oxidative stress [5,6]. Exposure to this element is associated, among others, with a decrease in IQ levels, disturbances in the processes related to learning capabilities and memory, as well as a deterioration of psychomotor skills [2,7,8]. It is recognised that long-term exposure to NaF results in an increase in dopamine levels in the striatum of rats as well as noradrenaline and serotonin levels in the hippocampus and neocortex [11,12]
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