Neuropsychopharmacology : official publication of the American College of NeuropsychopharmacologyApr 8, 2017

Alcohol Withdrawal May Increase Anxiety by Lowering Potassium Channel Activity in the Brain's Emotion Control Area

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

At 24 hours after ethanol withdrawal, the excitability of lateral habenula neurons was significantly increased in rats compared to ethanol naive rats.

Lateral habenula neurons exhibited a higher basal firing rate and excitability after ethanol withdrawal.
The amplitude of medium afterhyperpolarization was smaller in the lateral habenula of withdrawn rats.
M-type K-channels, which regulate neuronal activity, showed reduced currents and lower expression of their subunits in the lateral habenula post-withdrawal.
Increased anxiety levels were observed after ethanol withdrawal, which improved with inhibition of the lateral habenula.
Local infusion of an M-channel opener decreased both ethanol consumption and preference in the rats.

Simplified

Alcohol use disorders (AUDs) and anxiety disorders (ADs) are often seen concurrently, but their underlying cellular basis is unclear. For unclear reasons, the lateral habenula (LHb), a key brain region involved in the pathophysiology of ADs, becomes hyperactive after ethanol withdrawal. M-type Kchannels (M-channels), important regulators of neuronal activity, are abundant in the LHb, yet little is known about their role in AUDs and associated ADs. We report here that in rats at 24 h withdrawal from systemic ethanol administration (either by intraperitoneal injection, 2 g/kg, twice/day, for 7 days; or intermittent drinking 20% ethanol in a two-bottle free choice protocol for 8 weeks), the basal firing rate and the excitability of LHb neurons in brain slices was higher, whereas the amplitude of medium afterhyperpolarization and M-type Kcurrents were smaller, when compared to ethanol naive rats. Concordantly, M-channel blocker (XE991)-induced increase in the spontaneous firing rate in LHb neurons was smaller. The protein expression of M-channel subunits, KCNQ2/3 in the LHb was also smaller. Moreover, anxiety levels (tested in open field, marble burying, and elevated plus maze) were higher, which were alleviated by LHb inhibition either chemogenetically or by local infusion of the M-channel opener, retigabine. Intra-LHb infusion of retigabine also reduced ethanol consumption and preference. These findings reveal an important role of LHb M-channels in the expression of AUDs and ADs, and suggest that the M-channels could be a potential therapeutic target for alcoholics. + +

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Alcohol Withdrawal May Increase Anxiety by Lowering Potassium Channel Activity in the Brain's Emotion Control Area

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