Budziszewska B, Leśkiewicz M, Jaworska-Feil L, Lasoń W
Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Exp Clin Endocrinol Diabetes. 1999;107(1):75-9. doi: 10.1055/s-0029-1212077.
Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma corticosterone and testosterone levels were studied in male mice. Acute morphine administration (15 and 30 mg/kg i.p.) enhanced the corticosterone level after 1 and 2 hr (at a dose of 30 mg/kg only). A 4-day treatment with increasing doses of morphine, from 15 to 50 mg/kg i.p., increased the plasma corticosterone concentration at 2 hr after the last injection. Single administration of L-NAME (30 mg/kg i.p.) had no effect on the corticosterone level, whereas its repeated injections (30 mg/kg i.p., twice a day for four days) elevated the hormone concentration at 2 hr after the last dose. Pretreatment of mice with L-NAME enhanced the stimulatory effects of both acute and repeated morphine administration on the corticosterone level. D-NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor, had no effect on the morphine-induced changes in the corticosterone level. Acute morphine administration had no effect on the plasma testosterone level after 1 or 2 hr, whereas repeated drug injections decreased the hormone concentration after 2 hr. Single or repeated L-NAME administration did not influence the testosterone level in either control or morphine-treated animals. The above results indicate that inhibition of nitric oxide synthase enhances the stimulatory effect of morphine on corticosterone secretion, but does not influence the inhibitory effect of repeated morphine on the plasma testosterone concentration in mice.
在雄性小鼠中研究了一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯（L-NAME，30mg/kg腹腔注射）对吗啡诱导的血浆皮质酮和睾酮水平变化的影响。急性给予吗啡（15和30mg/kg腹腔注射）在1小时和2小时后（仅在30mg/kg剂量时）提高了皮质酮水平。用递增剂量的吗啡（从15mg/kg至50mg/kg腹腔注射）进行为期4天的治疗，在最后一次注射后2小时增加了血浆皮质酮浓度。单次给予L-NAME（30mg/kg腹腔注射）对皮质酮水平没有影响，而重复注射（30mg/kg腹腔注射，每天两次，共四天）在最后一剂后2小时提高了激素浓度。用L-NAME预处理小鼠增强了急性和重复给予吗啡对皮质酮水平的刺激作用。D-NAME（30mg/kg腹腔注射），一氧化氮合酶抑制剂的无活性形式，对吗啡诱导的皮质酮水平变化没有影响。急性给予吗啡在1小时或2小时后对血浆睾酮水平没有影响，而重复注射药物在2小时后降低了激素浓度。单次或重复给予L-NAME对对照组或吗啡处理组动物的睾酮水平均无影响。上述结果表明，抑制一氧化氮合酶增强了吗啡对皮质酮分泌的刺激作用，但不影响重复给予吗啡对小鼠血浆睾酮浓度的抑制作用。
