GABA-A receptor
What it is
Primary target of ethanol. GABA-A is a ligand-gated chloride channel; ethanol potentiates it at specific subunit configurations.
Ethanol’s action
- Positive allosteric modulator at GABA-A receptors containing α1 and δ subunits
- Increases chloride conductance → neuronal hyperpolarisation → CNS depression
- δ subunit receptors (extrasynaptic, high affinity) particularly sensitive at moderate doses
- α1 subunits mediate sedation, amnesia, ataxia — target of many hypnotics
Why it matters
GABA-A potentiation = acute intoxication (euphoria, motor impairment, sedation). Downstream:
- Suppresses REM early in the night
- Reduces anxiety at low doses
- At high doses: respiratory depression, blackout risk
Tolerance and withdrawal
- Chronic ethanol → GABA-A receptor downregulation and desensitisation
- Withdrawal = reduced GABAergic tone + glutamate NMDA rebound → hyperexcitability, seizures
- NMDA receptor antagonism by ethanol partially compensates during use; unmasked during withdrawal
Vitals implication
GABAergic signature during intoxication: HRV shifts toward sympathetic (LF/HF ↑), motor activity ↓, sedation visible in motion data.