CCKB拮抗剂对小鼠的抗抑郁样作用：纳曲吲哚的拮抗作用
Antidepressant-like effects of CCKB antagonists in mice: antagonism by naltrindole.
作者信息
Derrien M, Durieux C, Roques B P
机构信息
Departement de Pharmacochimie Moléculaire et Structurale, INSERM U266, CNRS URA D 1500, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
出版信息
Br J Pharmacol. 1994 Mar;111(3):956-60. doi: 10.1111/j.1476-5381.1994.tb14832.x.
Abstract
- The effects of selective CCKB agonists, BC 264 and BC 197 were investigated in the conditioned suppression of motility test in mice, an animal model used to select antidepressant drugs. The results showed that both CCKB agonists at doses of 3 and 30 micrograms kg-1, accentuated the suppression of motility in shocked mice and did not modify the behaviour of non-shocked mice. The effects of BC 264 were suppressed by L-365,260. 2. L-365,260 alone, at doses of 0.2 and 2 mg kg-1 decreased motor inhibition in shocked mice and had no effect in non-shocked mice. 3. The effects of L-365,260 observed in shocked mice were suppressed by naltrindole, a selective antagonist for delta-opioid receptors, suggesting the occurrence of physiological adverse interactions between CCK and opioid systems. 4. Together, these results suggest that CCKB antagonists could block centrally located CCKB receptors to produce antidepressant-like effects which could indirectly involve delta-opioid receptor stimulation.
摘要
- 在用于筛选抗抑郁药物的小鼠运动条件性抑制试验中，研究了选择性CCKB激动剂BC 264和BC 197的作用。结果表明，剂量为3和30微克/千克的两种CCKB激动剂均增强了电击小鼠的运动抑制，且未改变未电击小鼠的行为。L-365,260可抑制BC 264的作用。2. 单独使用剂量为0.2和2毫克/千克的L-365,260可降低电击小鼠的运动抑制，对未电击小鼠无影响。3. 纳曲吲哚（一种δ-阿片受体选择性拮抗剂）可抑制在电击小鼠中观察到的L-365,260的作用，提示CCK与阿片系统之间发生了生理性不良相互作用。4. 这些结果共同表明，CCKB拮抗剂可阻断位于中枢的CCKB受体以产生类抗抑郁作用，这可能间接涉及δ-阿片受体刺激。
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