Ethanol inhibition of lateral orbitofrontal cortex neuron excitability is mediated via dopamine D1/D5 receptor-induced release of astrocytic glycine

The ethanol inhibition of basolateral amygdala neuron spiking is mediated by a γ‐aminobutyric acid type A‐mediated tonic current

“…We reported previously that EtOH depolarized the membrane potential of astrocytes in the OFC leading to a glycine transporter GlyT1‐dependent efflux of glycine and activation of inhibitory strychnine‐sensitive glycine receptors on OFC pyramidal neurons. This was in contrast to a lack of effect of EtOH on mPFC neuron spike firing or the RMP of mPFC astrocytes (Nimitvilai‐Roberts et al, 2021). In this study, while EtOH decreased the spike firing of BLA neurons, it had no effect on the membrane potential of BLA astrocytes.…”

“…Astrocytes are known to regulate neuronal excitability and synaptic transmission in various brain regions (Araque et al, 1999) and impaired astrocyte activity is implicated in alcohol use disorder (Butterworth, 1995; de la Monte & Kril, 2014). Results from a recent study from our laboratory showed that EtOH, applied acutely, depolarized the membrane potential of OFC astrocytes and resulted in a reversal of the glycine transporter GlyT1, release of glycine and inhibition of OFC neuron excitability (Nimitvilai‐Roberts et al, 2021). To test whether EtOH produces a similar effect in the BLA, the membrane potential of sulforhodamine 101 (SR101) labeled astrocytes was monitored during exposure to EtOH (Figure 3C).…”

“…For example, at behaviorally relevant concentrations (11 to 66 mM), EtOH reduced current‐evoked firing of OFC neurons (Badanich et al, 2013), while 50 mM, but not 20 mM, of EtOH decreased excitability of thalamic neurons (Jia, Chandra, et al, 2008a). In contrast, higher concentrations of EtOH (66 to 100 mM) had no effect on evoked spiking neurons in the medial PFC (Nimitvilai‐Roberts et al, 2021; Tu et al, 2007). Region‐dependent differences in EtOH's effect on neuronal AP firing may be related to variable expression of EtOH‐sensitive ion channels and receptors that influence neuronal excitability such as those activated by GABA, glycine, and endocannabinoids, among others.…”

“…EtOH also inhibits AP firing of OFC neurons but this occurs via a novel glycine-dependent mechanism (Badanich et al, 2013;Nimitvilai-Roberts et al, 2021). In contrast, withdrawal from chronic EtOH increases spike firing and glutamatergic transmission of OFC neurons and eliminates the ability of acute EtOH to reduce firing (Nimitvilai et al, 2016).…”

“…For example, acute EtOH suppresses AP firing of neurons in the central amygdala (Naylor et al, 2001), likely via an increase in GABA A mediated currents (Roberto et al, 2003) while decreasing glutamatergic transmission (Roberto et al, 2004). EtOH also inhibits AP firing of OFC neurons but this occurs via a novel glycine‐dependent mechanism (Badanich et al, 2013; Nimitvilai‐Roberts et al, 2021). In contrast, withdrawal from chronic EtOH increases spike firing and glutamatergic transmission of OFC neurons and eliminates the ability of acute EtOH to reduce firing (Nimitvilai et al, 2016).…”