Glutamatergic neurotransmission is of particular interest in relation both to AD risk and its pharmacologic treatment. Glutamate, the most abundant excitatory neurotransmitter in the central nervous system, is involved in neuroproliferative, neurotoxic, neurodegenerative, and neuromodulatory processes, and is a key component of learning and memory (Kugaya and Sanacora 2005). Glutamatergic efferents from the prefrontal cortex, amygdala, and hippocampus innervate the cell bodies of the ventral tegmental area and the nucleus accumbens shell, facilitating dopaminergic transmission in these key areas of the “reward pathway” (Tzschentke and Schmidt 2003). Alcohol modulates glutamatergic neurotransmission, producing long-lasting neurobiological changes that may contribute to the symptoms of AD. The attenuation of these glutamatergic effects reduces alcohol-induced reward and relapse-like behavior in animals (Gass and Olive 2007). Further evidence of the importance of glutamatergic neurotransmission in AD comes from alcohol treatment trials of medications that modulate glutamatergic activity, including acamprosate (Kranzler and Gage 2008) and topiramate (Johnson et al., 2003, 2007).
