Effects of Acute Injection of Ethanol on the Mesolimbic Dopamine System in Freely Moving Rats
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Effects of Acute Injection of Ethanol on the Mesolimbic Dopamine System in Freely Moving Rats M. A. Mikhailova and R. R. Gainetdinov
Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 105, No. 7, pp. 853–860, July, 2019. Original article submitted April 4, 2019. Revised version received May 10, 2019. Accepted May 10, 2019. Alcohol is the third most important risk factor for disease in Russia and throughout the world. WHO data indicate that alcohol abuse kills 2.5 million people a year around the world, which is the population of a large city; of these, 600–700,000 occur in Russia. Despite the development of science and medicine, the mechanisms underlying the development of alcohol dependence remain unclear. An understanding of these mechanisms will help create novel approaches to the treatment of alcohol dependence. It is now known that the mesolimbic dopamine system plays a key role in forming addictive disorders, particularly alcohol dependence. Fast scanning cyclic voltammetry (FSCV) is a widely used method for studying dopamine. An advantage of this method is its high time and spatial resolution, making FSCV a powerful method for detecting changes in monoamine neurotransmitter concentrations in vivo. Our studies using FSCV in freely moving animals demonstrated that electrical stimulation of the ventral tegmental area (VTA) leads to detection of dopamine release in the nucleus accumbens (NAcc). We showed that acute ethanol injections (0.5 g/kg) lead to significant decreases in dopamine release in the NAcc induced by electrical stimulation of the VTA in freely moving rats. Use of the selective dopamine D2 autoreceptor antagonist raclopride significantly increased the measured signal, indicating that the incoming signal measured in the NAcc is dopaminergic rather than noradrenergic. Keywords: dopamine, voltammetry, alcoholism, ethanol.
Alcohol is the third most important risk factor for disease in Russia and throughout the world. WHO data indicate that alcohol abuse kills 2.5 million people a year around the world, which is the population of a large city; of these, 600–700,000 occur in Russia. At present, despite the development of science and medicine, the mechanisms of development of alcohol dependence remain incompletely understood; our understanding of the precise neural mechanisms responsible for the occurrence and development of alcohol dependence continues to be incomplete [1]. Advances in the development of effective methods for treating alcoholism and drug addiction depend on knowledge of the biological mechanisms underlying the formation of dependence. Ethanol is now known to affect the brain by modulating sev-
eral neurotransmitter systems, including but not restricted to GABA [2, 3], glutamate [4], serotonin [5], noradrenaline [6], vasopressin [7], adenosine [8], and dopamine (DA) [9–11]. It is now known that the mesolimbic dopamine system plays a key role in forming addictive disorders, particularly alcohol dependence [9, 10, 12–14]. It should be emphasized that the eff
