Table 3.
Potential Pharmacogenetic Targets Detected in Human Postmortem Brain Studies in Alcohol-Dependent Subjects and Animal Studies
| Potential Medication Targets | Altered Genes (Reference) | |
|---|---|---|
|
| ||
| Human Postmortem Studies | Animal Studies | |
| Acamproate | ↑NMDA subunit genes GRIN2B and GRIN2D in hippocampus (Enoch et al. 2014); ↓GRIN2D in the central amygdala (Jin et al. 2014); ↓GRIN2A in caudate n. (Bhandage et al. 2014) | ↓GRIN1 with chronic ethanol use in dorsolateral prefrontal cortex and ↑GRIN1-1 isoform and ↓GRIN1-2 isoform in OFC of male cynomolgus monkeys (Acosta et al. 2010). |
| Topiramate | ↑GRIA4 and GRIK3 in hippocampus (Enoch et al. 2014); ↓GRIA1, GRIA4, GRIK2, and GABRA2 in the central amygdala (Jin et al. 2014) | GRIA2 flop mRNA levels in OFC and GRIA3 flip and flop and GRIA4 flop mRNAs in DLPFC positively correlated with daily ethanol intake in male cynomolgus monkeys (Acosta et al. 2011). |
| Ondansetron (for association with QT interval prolongation)/Topiramate | ↓SCN4B in PFC (Farris et al. 2014) | ↑SCN4B in limbic areas in mice (Mulligan et al. 2006, Tabakoff et al. 2008) |
| Ondansetron/SSRIs | ↑TPH2 expression in dorsal and median raphe nuclei (Bach et al. 2014) | |
| Baclofen | ↓GABBR1 in cortex through intron 4 alternative mRNA splicing (Lee et al. 2014) and hippocampus (Enoch et al. 2012) | ↓GABBR1 in hippocampus in P rats (Enoch et al. 2012) |
| Naltrexone | ↑PDYN and PDYN in dorsolateral-PFC, OPRK1 in OFC and PDYN in hippocampus (Bazov et al. 2013) | ↓synaptosomal OPRK1 receptor expression in mesolimbic brain regions (Nizhnikov et al. 2014) in Sprague-Dawley rats; ↑POMC, PDYN and PENK in nucleus accumbens in rats (Bordner and Deak 2015); ↑PDYN amygdala and nucleus accumbens in rats (D'Addario et al. 2013; Lam et al. 2008) |
| Canabinoid | ↑CNR1 in PFC of suicidal alcoholics (Erdozain et al. 2014) | ↓CNR1 in caudate-putamen, ventro-medial nucleus of the hypothalamus, hippocampus and ↑ in dentate gyrus (Ortiz et al. 2004); ↓CNR1 in whole brain (Stringer et al. 2013) |
| Olanzapine | ↓DRD2 receptor protein levels in carriers of Taq1A polymorphism in the caudate nuclei (Noble et al. 1991) | ↓DRD2 in the nucleus accumbens and the hippocampus (Bice et al. 2008; Thanos et al. 2004) |
↑ upregulated genes; ↓ downregulated genes; OFC—orbitofrontal cortex; DLPFC—dorsolateral prefrontal cortex; PFC—prefrontal cortex.