Taurine enhances voluntary alcohol intake and promotes anxiolytic-like behaviors in rats
Introduction
Alcohol abuse is a serious public health problem, representing the third largest cause of illness in developed countries and the fifth leading cause of premature death and disability worldwide, accounting for about 4% of global mortality (World Health Organization, 2018). Alcohol exerts a positive modulator effect on γ-aminobutyric acid A receptors (GABAAR) and a negative effect on N-methyl-d-aspartate (NMDA) glutamatergic receptors (Gilpin & Koob, 2008; Roberto & Varodayan, 2017). Moreover, alcohol activates directly and indirectly the dopamine mesolimbic reward pathway (Brodie, Pesold, & Appel, 1999; Erdozain & Callado, 2011). Chronic use of high amounts of alcohol causes neuro-adaptive processes that change the reward system functionality, resulting in blunted dopamine transmission, which affects the motivation for alcohol use and may lead to addiction (Gilpin & Koob, 2008; Martinez et al., 2005; Roberto & Varodayan, 2017). Indeed, changes in the dopaminergic neuron activity in the ventral tegmental area (VTA) are correlated with extracellular levels of dopamine in the nucleus accumbens (NAc), and both are involved in the establishment of drug dependence, as well as susceptibility to relapse (Marinelli, Cooper, Baker, & White, 2003).
Alcohol consumption frequently occurs under social conditions in humans. However, most of the preclinical studies use socially isolated animals, limiting its translational value. The social environment in rodents differentially affects the acceptability of sensory properties of alcohol, the functionality of brain stress systems, alcohol voluntary intake and preference, and alcohol relapse behavior, depending on the age, sex, strain, and familiarity with other partners (Butler, Ariwodola, & Weiner, 2014; Eade, Youngentob, & Youngentob, 2016; Ryabinin & Walcott, 2018; Scott, Tjernström, & Roman, 2020). In this context, the use of pair-housed animals on a mesh-divided home cage could be an interesting alternative to enhance the social-dependent factors associated with alcohol drinking without losing the measurement of individual variabilities of consumption (Ryabinin & Walcott, 2018; Scott et al., 2020).
Taurine (2-aminoetanesulfonic acid), one of the constituents of energy drinks, is a β-amino acid found abundantly in the central nervous system (CNS) (Huxtable, 1992). It plays a role in several physiological processes, exerting osmoregulatory, anti-inflammatory, and antioxidant effects (Gu, Zhao, Qian, & Sun, 2015; Huxtable, 1992). Furthermore, in the CNS, taurine opens chloride channels in postsynaptic neurons by positive modulatory effects on GABAAR and glycine receptors (Albrecht & Schousboe, 2005), or by modulation of putative specific taurine receptors (Frosini et al., 2003). Taurine also acts directly as a partial antagonist on NMDA receptors, or acts indirectly by regulating intracellular calcium homeostasis, showing neuroprotection against glutamate-induced neuronal excitotoxicity (Chan et al., 2014; Wu et al., 2005).
Studies have shown that endogenous taurine levels increase in the amygdala and nucleus accumbens after alcohol administration in rats (Olive, 2002; Quertemont, Dahchour, Ward, & Witte, 1999). In addition, taurine antagonizes the behavioral effects of different alcohol exposure protocols in mice and zebrafish (Aragon, Trudeau, & Amit, 1992; Rosemberg et al., 2012) and restores the exploratory behavior that decreases after alcohol withdrawal in rats (Hansen et al., 2017). Acamprosate, a synthetic taurine derivative, is available for maintenance of abstinence in previously detoxified individuals. Similar to taurine, its effects have been attributed to interactions with GABAergic and glutamatergic neurotransmission (Dahchour & De Witte, 2000). Modulation of both systems may be an important target for attenuating the positive reinforcing effects caused by drugs of abuse, and may serve as a tool to promote abstinence and decrease relapse. Indeed, taurine pretreatment reduces acute alcohol consumption in rats (Olive, 2002). However, the effects of chronic taurine treatment on alcohol preference and consumption have not been explored. We hypothesize that taurine decreases alcohol intake and preference also after chronic treatment, and that taurine could be used as an anti-addictive drug. Thus, the aim of this study was to evaluate the effect of chronic taurine treatment on voluntary alcohol consumption and preference, as well as on some behaviors in rats.
Section snippets
Animals
Male adult Wistar (Rattus norvegicus) rats (~270 g), obtained from the Center for Reproduction and Experimentation of Laboratory Animals (CREAL-UFRGS, Porto Alegre, Brazil), were kept under a 12 h light/dark cycle (lights on at 7:00 AM) at 22 ± 1 °C and 55% air humidity. They were housed two per polypropylene cage (40 × 33 × 17.8 cm) divided longitudinally by a perforated aluminum grid, allowing free access to solutions and standard rat food (Nuvilab, Colombo, Brazil) (Fig. 1). All protocols
Alcohol consumption and preference
Our results showed that the Control group drank an average of 65 mL of fluids per day, while the Alcohol group consumed 100 mL of fluids per day (F(1,1728) = 365.67; p < 0.001). Vehicle solution consumption in the Alcohol group was similar to the Control group, and taurine treatment did not interfere in this consumption in both groups throughout the experiment.
Alcohol drinking preference was 30% in the Alcohol group before the taurine administration and remained unchanged in Alcohol/SAL
Discussion
Taurine treatment enhanced voluntary alcohol intake and preference in rats, contradicting our hypothesis. In addition, both acute and chronic taurine treatments produced anxiolytic-like behavior in alcohol-treated rats.
Curiously, the average alcohol consumption in both Alcohol/SAL and Alcohol/TAU groups was about 13 g/kg/day, representing twice the consumption obtained in a 2-bottle-choice voluntary model where the vehicle solution was water (Ericson, Ulenius, Adermark, & Söderpalm, 2017).
Credit author statement
Rianne Remus Pulcinelli: Conceptualization, Methodology, Formal analysis, Investigation, Visualization, Writing – Original Draft. Leonardo Fernandes de Paula: Investigation, Methodology, Data Curation, Formal analysis. Natália Azuaga Nietiedt: Investigation, Methodology, Data Curation, Formal analysis. Solange Bandiera: Conceptualization, Investigation, Methodology, Validation. Alana Witt Hansen: Investigation, Visualization, Writing – Original Draft. Lucas dos Reis Izolan: Resources, Writing –
Funding
This work was financially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Declaration of competing interest
None.
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