BACKGROUND: Alcohol use disorder (AUD) increases brain stress systems while suppressing reward system functioning. One expression of stress system recruitment is elevated GABAergic activity in the central amygdala (CeA), which is involved in the excessive drinking seen with AUD. The sulfonic amino acid taurine, a glycine receptor partial agonist, modulates GABAergic activity in the rewarding effects of alcohol. Despite taurine abundance in the amygdala, its role in the dysregulation of GABAergic activity associated with AUD has not been studied. Thus, here, we evaluated the effects of taurine on locally stimulated GABAergic neurotransmission in the CeA of naïve- and alcohol-dependent rats. METHODS: We recorded intracellularly from CeA neurons of naïve- and alcohol-dependent rats, quantifying locally evoked GABAA receptor-mediated inhibitory postsynaptic potentials (eIPSP). We examined the effects of taurine and alcohol on CeA eIPSP to characterize potential alcohol dependence-induced changes in the effects of taurine. RESULTS: We found that taurine decreased amplitudes of eIPSP in CeA neurons of naïve rats, without affecting the acute alcohol-induced facilitation of GABAergic responses. In CeA neurons from dependent rats, taurine no longer had an effect on eIPSP, but now blocked the ethanol (EtOH)-induced increase in eIPSP amplitude normally seen. Additionally, preapplication of the glycine receptor-specific antagonist strychnine blocked the EtOH-induced increase in eIPSP amplitude in neurons from naïve rats. CONCLUSIONS: These data suggest taurine may act to oppose the effects of acute alcohol via the glycine receptor in the CeA of naïve rats, and this modulatory system is altered in the CeA of dependent rats.
BACKGROUND:Alcohol use disorder (AUD) increases brain stress systems while suppressing reward system functioning. One expression of stress system recruitment is elevated GABAergic activity in the central amygdala (CeA), which is involved in the excessive drinking seen with AUD. The sulfonic amino acid taurine, a glycine receptor partial agonist, modulates GABAergic activity in the rewarding effects of alcohol. Despite taurine abundance in the amygdala, its role in the dysregulation of GABAergic activity associated with AUD has not been studied. Thus, here, we evaluated the effects of taurine on locally stimulated GABAergic neurotransmission in the CeA of naïve- and alcohol-dependent rats. METHODS: We recorded intracellularly from CeA neurons of naïve- and alcohol-dependent rats, quantifying locally evoked GABAA receptor-mediated inhibitory postsynaptic potentials (eIPSP). We examined the effects of taurine and alcohol on CeA eIPSP to characterize potential alcohol dependence-induced changes in the effects of taurine. RESULTS: We found that taurine decreased amplitudes of eIPSP in CeA neurons of naïve rats, without affecting the acute alcohol-induced facilitation of GABAergic responses. In CeA neurons from dependent rats, taurine no longer had an effect on eIPSP, but now blocked the ethanol (EtOH)-induced increase in eIPSP amplitude normally seen. Additionally, preapplication of the glycine receptor-specific antagonist strychnine blocked the EtOH-induced increase in eIPSP amplitude in neurons from naïve rats. CONCLUSIONS: These data suggest taurine may act to oppose the effects of acute alcohol via the glycine receptor in the CeA of naïve rats, and this modulatory system is altered in the CeA of dependent rats.
Authors: Larry Rodriguez; Dean Kirson; Sarah A Wolfe; Reesha R Patel; Florence P Varodayan; Angela E Snyder; Pauravi J Gandhi; Sophia Khom; Roman Vlkolinsky; Michal Bajo; Marisa Roberto Journal: Int J Mol Sci Date: 2022-07-16 Impact factor: 6.208
Authors: Sophia Khom; Larry Rodriguez; Pauravi Gandhi; Dean Kirson; Michal Bajo; Christopher S Oleata; Leandro F Vendruscolo; Barbara J Mason; Marisa Roberto Journal: Neurobiol Dis Date: 2022-01-04 Impact factor: 7.046