Timing Eclipses Amount: The Critical Importance of Intermittency in Alcohol Exposure Effects.

Frequency and duration of ethanol (EtOH) exposures influence the consequences of those experiences, with evidence building from basic science studies in rats and mice that intermittent alcohol access (IAA) typically produces a greater escalation of EtOH intake than more continuous alcohol access (CAA). IAA also better simulates human use patterns where alcohol levels typically clear from the body between periods of use. A variety of mechanisms have been proposed to contribute to the enhanced intake of EtOH induced by IAA, including a possible attenuation in the aversive effects of EtOH, although further studies are needed to address this and other possibilities. Neural differences include indications of an IAA-associated increase in NR2B receptors that is not evident with CAA; although little studied, alterations in other neural and neurotransmitter systems are evident as well. Many gaps in understanding of IAA/CAA effects remain. Further work is needed to characterize neural mechanisms underlying these effects, consequences of IAA/CAA on EtOH effects beyond intake, and the impact of stress and environmental variables on these differences. IAA/CAA studies to date have also largely been limited to males and to adult animals, and hence, more studies examining IAA/CAA across sex and age are needed. Such additional work is essential to determine unique contributors to IAA-induced elevations in EtOH intake that may provide important insights for the development of new prevention/intervention strategies for heavy alcohol use and abuse.