Endocannabinoids in striatal plasticity.

Endocannabinoids (eCBs) are lipid metabolites found throughout the nervous system that modulate synaptic plasticity mainly via actions on the cannabinoid 1 (CB1) receptor. Within the striatum, eCBs and CB1Rs initiate both short- and long-lasting synaptic depression at intrinsic GABAergic synapses and glutamatergic synapses made by cortical afferents. Recent studies have explored the mechanisms underlying eCB-mediated synaptic depression, and the role of this plasticity in striatal function. Dopamine (DA) and its receptors promote eCB-mediated depression of glutamatergic synapses, and dopamine depletion in animal models alters corticostriatal synapses in ways that may contribute to Parkinson's disease (PD). A growing body of literature indicates that alterations in eCB signaling occur in PD patients, suggesting possible therapeutic approaches targeting this neuromodulatory system.