Alcohol, as well as other drugs of abuse, produce long-term changes within the brain reward circuits and these changes are thought to lead to drug tolerance, reward dysfunction, escalation of drug intake, and eventually compulsive use (Russo et al., 2009). Research on the reward circuit has been centered on dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain and their projections to the limbic system, in particular the nucleus accumbens (NAc), dorsal striatum, amygdala, hippocampus, and regions of PFC (Robison and Nestler, 2011). Nevertheless, other neurotransmitter systems seem also to contribute to brain reward responses since animals can still exhibit positive hedonic responses in the absence of dopamine (Hyman et al., 2006). Ethanol as well as opioids, cannabinoids, and nicotine are thought to produce reward partially through non-dopaminergic mechanisms, e.g., μ opioid receptors expressed on NAc neurons, which appear to bypass dopamine inputs from the VTA (Hyman et al., 2006). Studies examining the effect of selective agonist and antagonist drugs have indicated that multiple neurotransmitters, including dopamine, serotonin, acetylcholine, glutamate, GABA, and various peptides, are involved in activation
