Clinical and basic research indicate that alcohol abuse and dependence are related to alterations in acetylcholine (ACh: Chatterjee and Bartlett, 2010; Davis and de Fiebre, 2006; Soderpalm et al., 2000), dopamine (DA: Heinz, 2002), gamma-aminobutyric-acid (GABA: Kumar et al., 2009; Maccioni and Colombo, 2009), glutamate (Davis and Wu, 2001; Gass and Olive, 2008), serotonin (5-HT: Engleman et al., 2008; Lovinger, 1999), opiate (Drews and Zimmer, 1997), neuropeptide-Y (NPY: Heilig and Thorsell, 2002), corticotropin releasing factor (CRF: Koob, 2010), substance P (George et al., 2008), nociceptin/orphanin FQ (NOP, N/OFQ: Economidou et al., 2008); ghrelin (Jerlhag et al., 2009, 2011a, 2011b); neurotrophic factors such as BDNF (Logrip et al., 2009), and hypothalamic-pituitary-adrenal (HPA: Gianoulakis et al., 1995; Keith et al., 1995; Rasmussen et al., 2002; Richardson et al., 2008) systems within the brain. Therefore, innate differences in these neuro-transmitter or neuromodulator systems between the high and low alcohol-consuming lines would suggest a role for these systems in their ethanol-preference phenotypes. Thus, rat animal models displaying these alcohol self-administration phenotypes (Table 2), and neurochemical phenotypes associated with alcohol abuse (Table 3), provide an ideal platform to evaluate the effectiveness of compounds (Table 4) targeting these neurochemical substrates to treat alcoholism.
