Downregulation of M-channels in lateral habenula mediates hyperalgesia during alcohol withdrawal in rats

Scientific Reports
Seungwoo KangJianghong Ye

Abstract

Hyperalgesia often occurs in alcoholics, especially during abstinence, yet the underlying mechanisms remain elusive. The lateral habenula (LHb) has been implicated in the pathophysiology of pain and alcohol use disorders. Suppression of m-type potassium channels (M-channels) has been found to contribute to the hyperactivity of LHb neurons of rats withdrawn from chronic alcohol administration. Here, we provided evidence that LHb M-channels may contribute to hyperalgesia. Compared to alcohol naïve counterparts, in male Long-Evans rats at 24-hours withdrawal from alcohol administration under the intermittent access paradigm for eight weeks, hyperalgesia was evident (as measured by paw withdrawal latencies in the Hargreaves Test), which was accompanied with higher basal activities of LHb neurons in brain slices, and lower M-channel protein expression. Inhibition of LHb neurons by chemogenetics, or pharmacological activation of M-channels, as well as overexpression of M-channels' subunit KCNQ3, relieved hyperalgesia and decreased relapse-like alcohol consumption. In contrast, chemogenetic activation of LHb neurons induced hyperalgesia in alcohol-naive rats. These data reveal a central role for the LHb in hyperalgesia during alcohol ...Continue Reading

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Citations

Jan 21, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Kevin R CoffeyJohn F Neumaier
Dec 17, 2019·Alcoholism, Clinical and Experimental Research·Scott EdwardsKatie Witkiewitz
Nov 5, 2020·International Journal of Molecular Sciences·Chaya ShorJiang-Hong Ye

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Methods Mentioned

BETA
electrophoresis

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Image Lab
Prism
GraphPad

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