Linking Ethanol-Addictive Behaviors With Brain Catecholamines: Release Pattern Matters

Abstract

Using a variety of animal models that simulate key features of the alcohol use disorder (AUD), remarkable progress has been made in identifying neurochemical targets that may contribute to the development of alcohol addiction. In this search, the dopamine (DA) and norepinephrine (NE) systems have been long thought to play a leading role in comparison with other brain systems. However, just recent development and application of optogenetic approaches into the alcohol research field provided opportunity to identify neuronal circuits and specific patterns of neurotransmission that govern the key components of ethanol-addictive behaviors. This critical review summarizes earlier findings, which initially disclosed catecholamine substrates of ethanol actions in the brain and shows how the latest methodologies help us to reveal the significance of DA and NE release changes. Specifically, we focused on recent optogenetic investigations aimed to reveal cause-effect relationships between ethanol-drinking (seeking and taking) behaviors and catecholamine dynamics in distinct brain pathways. These studies gain the knowledge that is needed for the better understanding addiction mechanisms and, therefore, for development of more effective AUD treatments. Based on the reviewed findings, new messages for researches were indicated, which may have broad applications beyond the field of alcohol addiction.

Applying a Fast-Scan Cyclic Voltammetry to Explore Dopamine Dynamics in Animal Models of Neuropsychiatric Disorders

“…Using FSCV recordings coupled with the selective optogenetic activation of dopamine VTA-nucleus accumbens circuitry, it was confirmed that high and low frequencies may generate phasic and tonic increases in dopamine release, respectively [46,47], which were previously detected in behaving animals [11][12][13]48]. This allowed Budygin's group to explore the relationship between dopamine transmission patterns and alcohol self-administration [49]. It has been revealed that phasic pattern of accumbal dopamine transmission within mesolimbic circuitry enhanced alcohol seeking, whereas tonic pattern inhibited alcohol-seeking and taking behaviors [47,50].…”

Behavioral and biochemical effects of alcohol withdrawal in female C3H/HeNRj and C57BL/6JRj mice

“…Despite extensive evidence on the dysregulation of dopaminergic, noradrenergic, and serotonergic signaling in AUD, we detected no significant changes in the concentrations of NE, DA, 5-HT, HVA, and 5-HIAA in both the striatum and hippocampus of C3H and B6 mice (Fitzgerald, 2013;Marcinkiewcz et al, 2016;Haass-Koffler et al, 2018;Khom et al, 2020;Grinevich et al, 2021). Notably, B6 alcohol-exposed mice displayed higher serotonin turnover in the hippocampus, as suggested by the increased 5-HIAA/5-HT ratio, measured indirectly, suggesting an alteration of the serotoninergic signaling.…”

“…Few studies reported similar outcomes in mice, including hypomagnesemia, hypophosphatemia and hypokalemia in the cerebellum and whole brain homogenates (Belknap et al, 1978;Te Riele and Verrips, 2014). Dopamine (DA), norepinephrine (NE) and 5-HT can all be altered in AUD and during withdrawal, with good concordance between human and rodent studies (Marcinkiewcz et al, 2016;Haass-Koffler et al, 2018;Grinevich et al, 2021). Conversely to a hyperdopaminergic state following acute alcohol exposure, chronic alcohol exposure and withdrawal result in a hypodopaminergic state that is thought to play a significant part in the neurotransmission mechanisms regulating alcohol dependence and relapse (Koob, 2003;Melis et al, 2005).…”

Auricular transcutaneous vagus nerve stimulation for alcohol use disorder: A chance to improve treatment?

“…Another study, including healthy participants, found that acute alcohol intake caused plasma NA to increase 30 min after consumption lasting approximately 4 h 51 . Acute alcohol significantly affects catecholamine dynamics, implying that continuous alcohol exposure might cause profound modulations in both DA and NA brain systems 52 . Animal experiments have shown that long‐term alcohol intake alters dorsal striatal dopamine release and uptake and the regulation of DA release by D2/3 dopamine autoreceptors in male but not female rhesus macaques 53 .…”