Chronic ethanol treatment and GABA(A) receptor α6 subunit gene expression: a study using α6 subunit-deficient mice

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Chronic alcohol consumption is known to alter GABA A receptor expression, particularly the α6 subunit in the cerebellum.
• This upregulation of the GABA A receptor α6 subunit has been implicated in the development of alcohol tolerance.

Purpose of the Study:

• To investigate whether the α6 gene is activated by chronic alcohol administration.
• To determine if functional α6 subunit-containing GABA(A) receptors are necessary for developing tolerance to ethanol's motor-impairing effects.

Main Methods:

• Utilized a genetically engineered mouse line lacking a functional α6 subunit but expressing β-galactosidase under the α6 gene promoter.
• Administered chronic ethanol to mice and assessed motor impairment using the rotarod test.
• Measured cerebellar β-galactosidase activity to evaluate α6 gene transcription.

Main Results:

• Chronic ethanol administration produced tolerance to motor impairment in the rotarod test.
• Ethanol treatment did not alter cerebellar β-galactosidase activity in α6 subunit-deficient mice.
• Tolerance to ethanol's motor effects was achieved in the absence of functional α6 subunit-containing GABA(A) receptors.

Conclusions:

• Tolerance to the motor-impairing effects of ethanol can occur independently of α6 subunit-containing GABA(A) receptors.
• The upregulation of α6 gene transcription by ethanol treatment appears to require the presence of functional α6 subunits.