多次注射κ-阿片受体激动剂U-50,488H对小鼠脑区和脊髓中一氧化氮合酶活性的影响。

Effect of multiple injections of U-50, 488H, a kappa-opioid receptor agonist, on the activity of nitric oxide synthase in brain regions and spinal cord of mice.

Bhargava H N, Kumar S

Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago, Health Sciences Center, Illinois 60612, USA.

Gen Pharmacol. 1997 Sep;29(3):397-9. doi: 10.1016/s0306-3623(96)00480-6.

Abstract

The time course of the effects of multiple injections of U-50,488H, a kappa-opioid receptor agonist, and its subsequent termination on its analgesic action and nitric oxide synthase (NOS) activity was determined in the brain regions and spinal cord of the mouse. 2. Male Swiss-Webster mice were rendered tolerant to U-50,488H by twice-daily injections of the drug (25 mg/kg, IP) for 4 days. Vehicle-injected mice served as controls. 3. In tolerant mice, NOS activity was unchanged in brain regions and the spinal cord after treatment with U-50,488H. During abstinence from U-50,488H, NOS activity was found to be increased in the cortex and remainder of the brain, but no change was noted in the cerebellum, midbrain and spinal cord. 4. These studies demonstrate that withdrawal from the short-term treatment with U-50,488H in mice causes induction of NOS in certain brain regions. However, long-term treatment and withdrawal from U-50,488H are not associated with changes in the central NOS activity and indicate a possible adaptation in the NOS activity.

摘要

确定了多次注射κ-阿片受体激动剂U-50,488H及其随后停药对小鼠脑区和脊髓镇痛作用及一氧化氮合酶（NOS）活性的影响的时间进程。2. 通过每天两次注射该药物（25 mg/kg，腹腔注射），持续4天，使雄性瑞士-韦伯斯特小鼠对U-50,488H产生耐受性。注射溶剂的小鼠作为对照。3. 在耐受性小鼠中，用U-50,488H治疗后，脑区和脊髓中的NOS活性未发生变化。在停用U-50,488H期间，发现皮质和脑的其余部分中NOS活性增加，但小脑、中脑和脊髓中未观察到变化。4. 这些研究表明，小鼠短期用U-50,488H治疗后停药会导致某些脑区中NOS的诱导。然而，长期用U-50,488H治疗及停药与中枢NOS活性的变化无关，表明NOS活性可能发生了适应性变化。