Welch S P, Bass P P, Olson K G, Pugh G
Department of Pharmacology and Toxicology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298.
Pharmacol Biochem Behav. 1992 Dec;43(4):1107-16. doi: 10.1016/0091-3057(92)90489-3.
Calcitonin gene-related peptide (CGRP) is a novel calcium-modulatory product of the gene that encodes for calcitonin. Acute administration of morphine decreases levels of CGRP in rat corpus striatum. Tolerance to morphine did not alter the levels of CGRP in any brain region or in the spinal cord of the rat. CGRP did not alter the tolerance to the antinociceptive effects of morphine. Chronic naltrexone increased the levels of CGRP in the hypothalamus. Concurrent chronic administration of naltrexone plus morphine raised the levels of CGRP in the medulla, midbrain, and spinal cord. CGRP enhances naloxone-precipitated withdrawal jumping in mice. In rats, during withdrawal the levels of CGRP were tripled in the corpus striatum and significantly reduced in the hippocampus and hypothalamus. In the corpus striatum, CGRP enhances forskolin-stimulated cyclic adenosine monophosphate (cAMP) accumulation when such accumulation is suppressed (as with the chronic opiate administration), but conversely depresses forskolin-stimulated cAMP accumulation under normal conditions (as with chronic vehicle administration). These data are consistent with the hypothesis that CGRP acts as a modulatory peptide in opiate-sensitive systems and tonic opioid control of CGRP levels exists in brain.
降钙素基因相关肽（CGRP）是一种由编码降钙素的基因产生的新型钙调节产物。急性给予吗啡可降低大鼠纹状体中CGRP的水平。对吗啡的耐受性并未改变大鼠任何脑区或脊髓中CGRP的水平。CGRP并未改变对吗啡镇痛作用的耐受性。慢性给予纳曲酮可增加下丘脑CGRP的水平。同时慢性给予纳曲酮加吗啡可提高延髓、中脑和脊髓中CGRP的水平。CGRP可增强小鼠中纳洛酮诱发的戒断跳跃反应。在大鼠中，戒断期间纹状体中CGRP的水平增加两倍，而海马体和下丘脑中的水平则显著降低。在纹状体中，当福斯高林刺激的环磷酸腺苷（cAMP）积累受到抑制时（如慢性给予阿片类药物时），CGRP可增强这种积累，但在正常条件下（如慢性给予赋形剂时），CGRP则会抑制福斯高林刺激的cAMP积累。这些数据与以下假设一致，即CGRP在阿片类药物敏感系统中作为一种调节肽起作用，并且大脑中存在对CGRP水平的紧张性阿片类药物控制。
