Fluoride Affects Dopamine Metabolism and Causes Changes in the Expression of Dopamine Receptors (D1R and D2R) in Chosen Brain Structures of Morphine-Dependent Rats

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.

The Effect of Prenatal and Neonatal Fluoride Exposure to Morphine-Induced Neuroinflammation

“…Previous studies have demonstrated that fluoride has an impact on morphine dependence and tolerance by influencing the levels and metabolism of dopamine in structures associated with dependence, as well as serotonin and norepinephrine in the hippocampus and neocortex. Additionally, it can modulate the expression of receptors for these monoamines [45,46]. This evidence highlights the potential of fluoride, as an environmental factor, to affect the state of dependence.…”

“…Our analysis suggests that fluoride pre-exposure influences the response to morphine administration in the hippocampus. Previous studies have shown that in rats perinatally treated with fluoride, morphine can decrease the expression of D1 and D2 receptors, as well as dopamine concentration in the hippocampus [45]. The impulses originating from hippocampal areas may stimulate the mesolimbic pathway [3,49], which is crucial in the initiation and development of dependence [3].…”

Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

“…Fluoride may be significantly dangerous to the human nervous system and have been known to penetrate the blood-brain barrier, where, through generation of free radicals, oxidative stress conditions are promoted, causing impaired function of myelin, neurons and neurotransmitters, associated with lower IQ scores, depression, disturbances in learning processes and psychomotor skills [7,[23][24][25]. Several studies have reported that fluoride can be toxic to the reproductive system causing decreased fertility [26,27] Recently, reports have indicated fluoride toxicity during immune and inflammatory responses and impaired glucose tolerance with insulin resistance in peripheral tissues [7].…”

Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours—A Research Hypothesis

“…Fluoride causes degenerative changes in all parts of the brain and in the spinal cord, including axon deterioration, myelin sheath degeneration, mitochondrial damage, and alterations in synaptic ultrastructure [ 56 , 60 ]. It also affects neurotransmitter metabolism and causes changes in the expression of neurotransmitter receptors [ 61 , 62 , 63 ]. Fluorine compounds impair energy metabolism of the brain, dependent primarily on the burning of glucose.…”