A more recent study demonstrates that a single dose of ethanol confers tolerance to a subsequent dose of THC, but pretreatment with a single dose of THC facilitates the ataxic effect of acute ethanol (da Silva et al., 2001). In a follow up to this study, rats that were given the CB1 antagonist SR 141716A (SR) with ethanol on the first day failed to develop tolerance to the ataxic effects of ethanol the following day, but SR treatment did not affect acute tolerance that develops within a single administration of ethanol (Lemos et al., 2007). Recent findings from our lab suggest a similar tolerance phenomenon is present for other behavioral measures as well. Mice treated chronically with ethanol for ten consecutive days displayed significantly reduced sensitivity to cannabinoid-induced hypomotility, hypothermia, and antinociception that was correlated with changes in CB1 receptor expression in the periaqueductal grey, hypothalamus, and ventral tegmental area (Pava et al., 2012). Importantly, cannabinoid-induced catalepsy was not altered by ethanol pre-treatment suggesting the modulation of CB1 function by ethanol is region or at least circuit specific. Together the
