Ethanol also alters another major form of synaptic plasticity in the dorsal striatum, namely long-term synaptic depression (LTD) (Xia, Li et al. 2006, Adermark, Talani et al. 2009, Adermark, Jonsson et al. 2011, DePoy, Daut et al. 2013). The mechanism of LTD induction and expression in DS involves a retrograde trans-synaptic mechanism driven by neuromodulators known as endocannabinoids (eCBs). The eCBs are lipid metabolites that are ubiquitous in the brain and body. Within the brain the eCBs primarily activate the cannabinoid 1 (CB1) subtype of G protein-coupled receptor (GPCR), the major molecular target of delta-9-tetrahydrocannabinol which is the predominant psychoactive ingredient in drugs derived from Cannabis sativa (e.g. marijuana, hashish, spice). This receptor is found predominantly on presynaptic axon terminals where it suppresses neurotransmitter release. Within the striatum, eCBs participate in LTD at both GABAergic and glutamatergic synapses (Calabresi, Maj et al. 1992, Gerdeman, Ronesi et al. 2002, Adermark, Talani et al. 2009, Mathur, Capik et al. 2011). The glutamatergic synapses that express LTD are made by afferents from the cortex, as these inputs, but not thalamic inputs, contain CB1
