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

We examined whether acetylcholine release in the hippocampus and striatum and noradrenaline release in the hippocampus is altered in CB1 receptor-de®cient mice. The electrically evoked tritium over¯ow from hippocampal slices preincubated with [3 H]-choline was increased by about 100% in CB1 7/7 compared to CB1 +/+ mice whereas the electrically evoked tritium over¯ow from striatal slices preincubated with [3 H]-choline and from hippocampal slices preincubated with [3 H]- noradrenaline did not di€er. The cannabinoid receptor agonist, WIN 55,212-2, inhibited, and the CB1 receptor antagonist, SR 141716, facilitated, the evoked tritium over¯ow from hippocampal slices (preincubated with [3 H]-choline) from CB1 +/+ as opposed to CB1 7/7 mice. Both drugs did not a€ect the evoked tritium over¯ow from striatal slices (preincubated with [3 H]-choline) and from hippocampal slices (preincubated with [3 H]-noradrenaline) from CB1 +/+ and CB1 7/7 mice. The selective increase in acetylcholine release in CB1 7/7 mice may indicate that the presynaptic CB1 receptors on the cholinergic neurones of the mouse hippocampus are tonically activated and/or constitutively active in vivo.