MODULATION OF ELECTRICALLY EVOKED ACETYLCHOLINE RELEASE THROUGH CANNABINOID CB1 RECEPTORS: EVIDENCE FOR AN ENDOCANNABINOID TONE IN THE HUMAN NEOCORTEX

many Abstract—Cannabinoids are known to inhibit neurotransmit-ter release in the CNS through CB1 receptors. The present study compares the effects of synthetic cannabinoids on acetylcholine (ACh) release in human and mice neocortex. We further investigated a possible endocannabinoid tone on CB1 receptors in human neocortex caused by endogenous agonists like anandamide or 2-arachidonylglycerol. Brain slices, incubated with [3H]-choline, were superfused and stimulated electrically under autoinhibition-free condi-tions to evoke tritium overflow assumed to represent ACh release. The first series of experiments was performed with 26 pulses, 60 mA, at 0.1 Hz. In mice neocortical slices, the cannabinoid receptor agonist WIN55212-2 decreased ACh release (pIC506.68, Imax67%). In the human neocortex th