Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain: preliminary findings

A number of studies in rodents have shown various effects of alcohol (ethanol) administration on the catecholaminergic neurotransmitters, norepinephrine (NE) and dopamine (DA). These studies suggest that presentation of alcohol to mice or rats can alter brain levels of NE and DA, in various subregions. Three previous publications (Fitzgerald 2012, 2020, 2022) have presented the hypothesis that there may be an unidentified pathway in rodents, and other organisms, that actually transforms ethanol to NE or DA. Here, this paper investigates the hypothesis in male CD-1 mice. Experimental mice were systemically injected with an intoxicating dose of stable isotope-labeled carbon 13 (C13) ethanol (ethanol-1-13C, 20% v/v, 1.5 g/kg, i.p.), and brain samples (hippocampus and brainstem) were collected two hours post-injection. Two other groups of mice received normal unlabeled carbon 12 (C12) ethanol or a water (Control) injection, respectively. Although we had difficulty detecting the two neurotransmitters (especially C13 NE) due to their very low concentrations, high resolution mass spectrometry analysis suggests that C12 ethanol selectively boosted hippocampal C12 NE, and C13 ethanol likewise boosted hippocampal C13 NE. We did not observe effects on DA. These data provide preliminary information on whether there is a novel biosynthetic pathway in mice that converts alcohol to catecholamines in select brain regions, where the ethanol molecule would presumably lead to formation of the ethanolamine side chain of NE. There are, however, alternative interpretations of these findings, including that acute alcohol administration modulates catecholamine release, reuptake, metabolism, or canonical biosynthesis.