Activation of CB1 cannabinoid receptors inhibits neurotransmitter release from identified synaptic sites in rat hippocampal cultures

The effects of cannabinoids on synaptic transmission were measured opticall y in rat hippocampal cultures. Synaptic release sites were labeled with the fluorescent dye FM1-43 in a stimulus-dependent manner. Action potential-in duced release of FM1-43 required extracellular Ca2+ and was inhibited 65 +/ - 3% by blockade of high-threshold voltage-gated Ca2+ channels with omega-g rammotoxin SIA (300 nM). The cannabimimetic drug, Win 55212-2 (300 nM), inh ibited FM1-43 release by 51 +/- 3%. The inhibition produced by Win55212-2 w as blocked by the CB1 cannabinoid receptor antagonist, SR141716 (1 mu M). T he intensity of FM1-43 labeled puncta ranged 4-fold, although the inhibitio n produced by Win55212-2 was distributed normally across synaptic sites of various labeling intensities. The FM1-43-based optical method appears promi sing for the study of the effects of cannabinoids and other drugs on synapt ic networks. These results indicate that cannabimimetics act presynapticall y to inhibit the release of neurotransmitter and that this inhibition is ob served uniformly at boutons of varied activity levels. (C) 2000 Elsevier Sc ience B.V. All rights reserved.