EFFECT OF THE CANNABINOID RECEPTOR SPECT AGENT, AM-281, ON HIPPOCAMPAL ACETYLCHOLINE-RELEASE FROM RAT-BRAIN SLICES

The SPECT ligand AM 281, a less lipophilic analog of the cannabinoid r eceptor antagonist SR 141716A, robustly potentiated electrically-evoke d release of acetylcholine from superfused hippocampal slices and prev ented the inhibition of acetylcholine release by the cannabimimetic dr ug WIN 55212-2. These results, similar to earlier observations with SR 141716A, indicate that AM 281 is either a cannabinoid receptor antago nist or inverse agonist. Despite showing lower affinity than SR 141716 A in hippocampal membrane binding experiments, AM 281 had slightly gre ater potency than SR 141716A in the hippocampal slice experiments, per haps because of reduced drug absorption to slice membranes and to the apparatus. (C) 1997 Elsevier Science Ireland Ltd.