Enhanced acetylcholine release in the hippocampus of cannabinoid CB1 receptor-deficient mice

We examined whether acetylcholine release in the hippocampus and striatum a nd noradrenaline release in the hippocampus is altered in CB1 receptor-defi cient mice. The electrically evoked tritium overflow from hippocampal slice s preincubated with [H-3]-choline was increased by about 100% in CB1-/- com pared to CB1+/+ mice whereas the electrically evoked tritium overflow from striatal slices preincubated with [H-3]-choline and from hippocampal slices preincubated With [H-3]-noradrenaline did not differ. The cannabinoid rece ptor agonist, WIN 55,212-2, inhibited, and the CB1 receptor antagonist, SR 141716, facilitated, the evoked tritium overflow from hippocampal slices (p reincubated with [H-3]-choline) from CB1+/+ as opposed to CB1-/- mite. Both drugs did not affect the evoked tritium overflow from striatal slices (pre incubated with [H-3]-choline) and from hippocampal slices (preincubated wit h [H-3]-noradrenaline) from CB1+/+ and CB1-/- mice. The selective increase in acetylcholine release in CB1-/- mice may indicate that the presynaptic C B1 receptors on the cholinergic neurones of the mouse hippocampus are tonic ally activated and/or constitutively active in vivo.