The results demonstrating altered CB1 expression following withdrawal from chronic ethanol beg the question of what effect reduced CB1 signaling has on the neuroadaptions occurring through withdrawal. One effect of the down-regulation in CB1 may be to counteract neuroadaptations at GABAergic and glutamatergic synapses following chronic ethanol consumption. Warnault et al (2007) observed that CB1 KO mice did not exhibit the chronic ethanol-induced changes in cortical, hippocampal, and cerebellar NMDA and GABAA receptor expression found in wt mice. However, future studies utilizing conditional knockouts, CB1 antagonists, or genetic knockdown experiments would be useful to determine if this observation is due to developmental mechanisms specific to constitutive knockouts.
