NeuropharmacologyJun 30, 2019

Activating calming receptors in the brain's decision area reduces anxiety, depression, and drinking in rats after alcohol withdrawal

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Rats undergoing alcohol withdrawal exhibited higher anxiety and stress sensitivity compared to alcohol-naïve rats.

Intra-LHb injection of glycine reduced anxiety and alcohol intake in withdrawal rats.
The effects of glycine were blocked by strychnine, indicating involvement of glycine receptors.
Strychnine administration in alcohol-naïve rats induced anxiety- and depression-like behaviors.
Withdrawal rats showed lower frequency and amplitude of spontaneous inhibitory postsynaptic currents in LHb neurons.
Strychnine application caused depolarization and increased action potential firing in LHb neurons.
Glycine and sarcosine decreased LHb activity, suggesting glycine's role in inhibiting hyperactivity in LHb under various conditions.

Simplified

The lateral habenula (LHb) is activated by a range of aversive states including those related to alcohol withdrawal and has glycine receptors (GlyRs), a sensitive target of alcohol. However, whether GlyRs in the LHb contribute to alcohol-related behaviors is unknown. Here, we report that rats experiencing withdrawal from chronic alcohol consumption showed higher anxiety and sensitivity to stress compared to their alcohol-naïve counterparts. Intra-LHb injection of glycine attenuated these aberrant behaviors and reduced alcohol intake upon alcohol re-access. Glycine's effect was blocked by strychnine, a GlyR antagonist, indicating that it was mediated by strychnine-sensitive GlyRs. Conversely, intra-LHb strychnine elicited anxiety- and depression-like behaviors in Naïve rats but not in withdrawal rats. Additionally, both the frequency and the amplitude of the spontaneous IPSCs were lower in LHb neurons in slices of withdrawal rats compared to naïve rats. Also, there were sporadic strychnine-sensitive synaptic events in some LHb neurons. Bath perfusion of strychnine induced a depolarizing inward current and increased action potential firings in LHb neurons. By contrast, bath perfusion of glycine or sarcosine, a glycine transporter subtype 1 inhibitor, inhibited LHb activity. Collectively, these data reveal that LHb neurons are under the tonic glycine inhibition both in physiological and pathological conditions. Activation of GlyRs reverses LHb hyperactivity, alleviates aberrant behaviors, and reduces alcohol intake, thus highlighting the GlyRs in the LHb as a potential therapeutic target for alcohol-use disorders.

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Activating calming receptors in the brain's decision area reduces anxiety, depression, and drinking in rats after alcohol withdrawal

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