Scn4b regulates the hypnotic effects of ethanol and other sedative drugs

Yuri A. Blednov, Michal Bajo, Amanda J. Roberts, Adriana J. Da Costa, Mendy Black, Stephanie Edmunds, Jody Mayfield, Marisa Roberto, Gregg E. Homanics, Amy W. Lasek, Robert Hitzemann, Robert A. Harris

Research output: Contribution to journalArticle

Abstract

The voltage-gated sodium channel subunit β4 (SCN4B) regulates neuronal activity by modulating channel gating and has been implicated in ethanol consumption in rodent models and human alcoholics. However, the functional role for Scn4b in ethanol-mediated behaviors is unknown. We determined if genetic global knockout (KO) or targeted knockdown of Scn4b in the central nucleus of the amygdala (CeA) altered ethanol drinking or related behaviors. We used four different ethanol consumption procedures (continuous and intermittent two-bottle choice (2BC), drinking-in-the dark and chronic intermittent ethanol vapor) and found that male and female Scn4b KO mice did not differ from their wild-type (WT) littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter 2BC ethanol drinking. However, Scn4b KO mice showed longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital and ketamine. KO mice showed slower recovery to basal levels of handling-induced convulsions after ethanol injection, which is consistent with the increased sedative effects observed in these mice. However, Scn4b KO mice did not differ in the severity of acute ethanol withdrawal. Acoustic startle responses, ethanol-induced hypothermia and clearance of blood ethanol also did not differ between the genotypes. There were also no functional differences in the membrane properties or excitability of CeA neurons from Scn4b KO and WT mice. Although we found no evidence that Scn4b regulates ethanol consumption in mice, it was involved in the acute hypnotic effects of ethanol and other sedatives.

Original languageEnglish (US)
Article numbere12562
JournalGenes, Brain and Behavior
DOIs
StatePublished - Jan 1 2019

Fingerprint

Hypnotics and Sedatives
Ethanol
Pharmaceutical Preparations
Knockout Mice
Drinking
Startle Reflex
Righting Reflex
Voltage-Gated Sodium Channels
Induced Hypothermia
Ketamine
Pentobarbital
Alcoholics
Acoustics
Rodentia
Seizures
Genotype

Keywords

  • acute withdrawal
  • alcohol
  • central amygdala neurons
  • chronic intermittent ethanol vapor
  • drinking-in-the dark
  • knockout mice
  • loss of righting reflex
  • sedatives
  • sodium channel subunit Scn4b
  • two-bottle choice ethanol drinking

ASJC Scopus subject areas

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Blednov, Y. A., Bajo, M., Roberts, A. J., Da Costa, A. J., Black, M., Edmunds, S., ... Harris, R. A. (2019). Scn4b regulates the hypnotic effects of ethanol and other sedative drugs. Genes, Brain and Behavior, [e12562]. https://doi.org/10.1111/gbb.12562

Scn4b regulates the hypnotic effects of ethanol and other sedative drugs. / Blednov, Yuri A.; Bajo, Michal; Roberts, Amanda J.; Da Costa, Adriana J.; Black, Mendy; Edmunds, Stephanie; Mayfield, Jody; Roberto, Marisa; Homanics, Gregg E.; Lasek, Amy W.; Hitzemann, Robert; Harris, Robert A.

In: Genes, Brain and Behavior, 01.01.2019.

Research output: Contribution to journalArticle

Blednov, YA, Bajo, M, Roberts, AJ, Da Costa, AJ, Black, M, Edmunds, S, Mayfield, J, Roberto, M, Homanics, GE, Lasek, AW, Hitzemann, R & Harris, RA 2019, 'Scn4b regulates the hypnotic effects of ethanol and other sedative drugs', Genes, Brain and Behavior. https://doi.org/10.1111/gbb.12562
Blednov YA, Bajo M, Roberts AJ, Da Costa AJ, Black M, Edmunds S et al. Scn4b regulates the hypnotic effects of ethanol and other sedative drugs. Genes, Brain and Behavior. 2019 Jan 1. e12562. https://doi.org/10.1111/gbb.12562
Blednov, Yuri A. ; Bajo, Michal ; Roberts, Amanda J. ; Da Costa, Adriana J. ; Black, Mendy ; Edmunds, Stephanie ; Mayfield, Jody ; Roberto, Marisa ; Homanics, Gregg E. ; Lasek, Amy W. ; Hitzemann, Robert ; Harris, Robert A. / Scn4b regulates the hypnotic effects of ethanol and other sedative drugs. In: Genes, Brain and Behavior. 2019.
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abstract = "The voltage-gated sodium channel subunit β4 (SCN4B) regulates neuronal activity by modulating channel gating and has been implicated in ethanol consumption in rodent models and human alcoholics. However, the functional role for Scn4b in ethanol-mediated behaviors is unknown. We determined if genetic global knockout (KO) or targeted knockdown of Scn4b in the central nucleus of the amygdala (CeA) altered ethanol drinking or related behaviors. We used four different ethanol consumption procedures (continuous and intermittent two-bottle choice (2BC), drinking-in-the dark and chronic intermittent ethanol vapor) and found that male and female Scn4b KO mice did not differ from their wild-type (WT) littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter 2BC ethanol drinking. However, Scn4b KO mice showed longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital and ketamine. KO mice showed slower recovery to basal levels of handling-induced convulsions after ethanol injection, which is consistent with the increased sedative effects observed in these mice. However, Scn4b KO mice did not differ in the severity of acute ethanol withdrawal. Acoustic startle responses, ethanol-induced hypothermia and clearance of blood ethanol also did not differ between the genotypes. There were also no functional differences in the membrane properties or excitability of CeA neurons from Scn4b KO and WT mice. Although we found no evidence that Scn4b regulates ethanol consumption in mice, it was involved in the acute hypnotic effects of ethanol and other sedatives.",
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AU - Black, Mendy

AU - Edmunds, Stephanie

AU - Mayfield, Jody

AU - Roberto, Marisa

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AU - Hitzemann, Robert

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AB - The voltage-gated sodium channel subunit β4 (SCN4B) regulates neuronal activity by modulating channel gating and has been implicated in ethanol consumption in rodent models and human alcoholics. However, the functional role for Scn4b in ethanol-mediated behaviors is unknown. We determined if genetic global knockout (KO) or targeted knockdown of Scn4b in the central nucleus of the amygdala (CeA) altered ethanol drinking or related behaviors. We used four different ethanol consumption procedures (continuous and intermittent two-bottle choice (2BC), drinking-in-the dark and chronic intermittent ethanol vapor) and found that male and female Scn4b KO mice did not differ from their wild-type (WT) littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter 2BC ethanol drinking. However, Scn4b KO mice showed longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital and ketamine. KO mice showed slower recovery to basal levels of handling-induced convulsions after ethanol injection, which is consistent with the increased sedative effects observed in these mice. However, Scn4b KO mice did not differ in the severity of acute ethanol withdrawal. Acoustic startle responses, ethanol-induced hypothermia and clearance of blood ethanol also did not differ between the genotypes. There were also no functional differences in the membrane properties or excitability of CeA neurons from Scn4b KO and WT mice. Although we found no evidence that Scn4b regulates ethanol consumption in mice, it was involved in the acute hypnotic effects of ethanol and other sedatives.

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