Chunk #0 — A Multi-level, Integrative Analysis of Ethanol’s Effects on the Nervous System: Bottom-Up and Top-Down Approaches to Finding Ethanol Targets
Ethanol distribution in the body and brain is similar to water, with equilibration throughout organs and cells within a few minutes of drinking. This property contributed to the idea that many of ethanol’s effects involve its occupation of water-filled cavities in proteins and subsequent alteration of function. Considering the ubiquity of distribution and low drug potency, ethanol acts on numerous molecular targets in neurons and synapses throughout the brain. This lack of specificity can be daunting to those who study potent and specific drugs, including drugs of abuse with circumscribed primary molecular targets (e.g., opiates). However, even these target-specific drugs produce complex secondary neuroadaptations that contribute to drug use disorders. It is worth noting that the function of many molecules in mammalian neurons appears to be remarkably insensitive to ethanol (Yamakura et al., 2001). Thus, earlier ideas about ubiquitous molecular effects due to changes in membrane fluidity are not helpful in understanding how ethanol alters neuronal function (Peoples et al., 1996). Even if fluidity changes occur, these changes lead to altered neuronal function, and thus, we must examine the proteins
