EXAMINATION OF THE EFFECT OF THE CANNABINOID RECEPTOR AGONIST, CP-55,940, ON ELECTRICALLY-EVOKED TRANSMITTER RELEASE FROM RAT-BRAIN SLICES

In the present study we examined the effect of the cannabinoid recepto r agonist, -[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol; CP 55,94 0} on [C-14]acetylcholine and [H-3]norepinephrine release from hippoca mpal slices and on [C-14]acetylcholine release from striatal slices. C P 55,940 potently inhibited electrically evoked [C-14]acetylcholine re lease from hippocampal slices, with an EC50 of 0.02 mu M and a maximal inhibition of 61% at 1 mu M The inhibition of acetylcholine release b y CP 55.940 was partially antagonized (60%) by the cannabinoid recepto r antagonist, ichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide hydro chloride; SR 141716A}. Alone, SR 141716A significantly enhanced stimul ated [C-14]acetylcholine release. In contrast to the effects of CP 55, 940 on [C-14]acetylcholine release, electrically evoked [H-3]norepinep hrine release from hippocampal slices and [C-14]acetylcholine release from striatal slices were both unaffected by this compound. Similarly, hippocampal [H-3]norepinephrine release and striatal [C-14]acetylchol ine release were not affected by SR 141716A. In conclusion, the result s of this study extend our previous data indicating that cannabinoid r eceptors modulate acetylcholine release in the hippocampus. The effect s of cannabinoid receptor activation on [H-3]acetylcholine release in the hippocampus does not appear to extend to [H-3]norepinephrine relea se from this region or to acetylcholine release from the striatum. (C) 1997 Elsevier Science B.V.