Chunk #39 — Methods — Glial cell-mediated glutamatergic dysfunction in co-occurring SUDs and depression — Ketamine as a glutamatergic probe in comorbidity
In addition to shared glial cell dysfunction, several studies conducted with the NMDA receptor antagonist ketamine support shared glutamatergic dysregulation in comorbid depression and SUDs (Miguel-Hidalgo et al. 2010). Ketamine recreates ethanol-like effects in recently detoxified alcoholics in a dose-dependent manner, which more closely resembles alcohol’s sedative rather than euphoric effects (Krystal et al. 1998). Recently detoxified alcoholics also display fewer dissociative-like symptoms, acute dysphoria, or cognitive/executive dysfunction during ketamine administration relative to non-dependent controls, suggesting that chronic alcohol-induced NMDA receptor antagonism attenuates ketamine’s adverse effects (Krystal et al. 2003). Alcohol-dependent patients may also not experience the negative cognitive and psychological signals to stop drinking beyond the point of mild-to-moderate intoxication (Krystal et al. 2003). Even non-dependent individuals with a family history of alcohol dependence display a more blunted response to ketamine than subjects without this genetic loading (Petrakis et al. 2004).
