Scn4b regulates the hypnotic effects of ethanol and other sedative drugs
| Autor: | Adriana Da Costa, Amy W. Lasek, Amanda J. Roberts, Robert Hitzemann, Jody Mayfield, Gregg E. Homanics, Michal Bajo, Yuri A. Blednov, R. A. Harris, Marisa Roberto, Stephanie Edmunds, Mendy Black |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Pentobarbital Alcohol Drinking medicine.drug_class Article 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Internal medicine Reflex Genetics medicine Premovement neuronal activity Animals Hypnotics and Sedatives Ethanol Voltage-Gated Sodium Channel beta-4 Subunit Chemistry Central nucleus of the amygdala Hypothermia Amygdala Mice Inbred C57BL 030104 developmental biology Endocrinology Neurology Sedative Knockout mouse Barbiturates Female medicine.symptom 030217 neurology & neurosurgery Gaboxadol medicine.drug |
| Zdroj: | Genes Brain Behav |
| ISSN: | 1601-183X |
| Popis: | 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 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, drinking-in-the dark, and chronic intermittent ethanol vapor) and found that male and female Scn4b knockout mice did not differ from their wild-type littermates in ethanol consumption in any of the tests. Knockdown of Scn4b mRNA in the CeA also did not alter two-bottle choice ethanol drinking. However, Scn4b knockout mice demonstrated longer duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital, and ketamine. Knockout 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 knockout 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 knockout and wild-type 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|