Kathmann M, Weber B, Zimmer A, Schlicker E
Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Reuterstr. 2b, 53113 Bonn, Germany.
Br J Pharmacol. 2001 Mar;132(6):1169-73. doi: 10.1038/sj.bjp.0703987.
We examined whether acetylcholine release in the hippocampus and striatum and noradrenaline release in the hippocampus is altered in CB(1) receptor-deficient mice. The electrically evoked tritium overflow from hippocampal slices preincubated with [(3)H]-choline was increased by about 100% in CB(1)(-/-) compared to CB(1)(+/+) mice whereas the electrically evoked tritium overflow from striatal slices preincubated with [(3)H]-choline and from hippocampal slices preincubated with [(3)H]-noradrenaline did not differ. The cannabinoid receptor agonist, WIN 55,212-2, inhibited, and the CB(1) receptor antagonist, SR 141716, facilitated, the evoked tritium overflow from hippocampal slices (preincubated with [(3)H]-choline) from CB(1)(+/+) as opposed to CB(1)(-/-) mice. Both drugs did not affect the evoked tritium overflow from striatal slices (preincubated with [(3)H]-choline) and from hippocampal slices (preincubated with [(3)H]-noradrenaline) from CB(1)(+/+) and CB(1)(-/-) mice. The selective increase in acetylcholine release in CB(1)(-/-) mice may indicate that the presynaptic CB(1) receptors on the cholinergic neurones of the mouse hippocampus are tonically activated and/or constitutively active in vivo.
我们研究了CB(1)受体缺陷型小鼠海马体和纹状体中乙酰胆碱的释放以及海马体中去甲肾上腺素的释放是否发生改变。与CB(1)(+/+)小鼠相比，用[(3)H]-胆碱预孵育的海马切片经电刺激诱发的氚溢出在CB(1)(-/-)小鼠中增加了约100%，而用[(3)H]-胆碱预孵育的纹状体切片以及用[(3)H]-去甲肾上腺素预孵育的海马切片经电刺激诱发的氚溢出并无差异。大麻素受体激动剂WIN 55,212-2抑制了CB(1)(+/+)小鼠（而非CB(1)(-/-)小鼠）海马切片（用[(3)H]-胆碱预孵育）经电刺激诱发的氚溢出，而CB(1)受体拮抗剂SR 141716则起到了促进作用。这两种药物均未影响CB(1)(+/+)和CB(1)(-/-)小鼠纹状体切片（用[(3)H]-胆碱预孵育）以及海马切片（用[(3)H]-去甲肾上腺素预孵育）经电刺激诱发的氚溢出。CB(1)(-/-)小鼠中乙酰胆碱释放的选择性增加可能表明，小鼠海马体胆碱能神经元上的突触前CB(1)受体在体内处于紧张性激活状态和/或组成性激活状态。
