Negri L, Noviello V, Angelucci F
Institute of Medical Pharmacology, University La Sapienza, Rome, Italy.
Eur J Pharmacol. 1991 Dec 17;209(3):163-8. doi: 10.1016/0014-2999(91)90165-m.
When given i.c.v. in rats deltorphins induced a syndrome of behavioural stimulation consisting of increased locomotion rearing and sniffing. The increased locomotor activity and rearing were dose-related over the range of 0.13 to 3.8 nmol/rat for [D-Ala2]deltorphin II (DADELT II) and 1.04 to 20.8 nmol/rat for deltorphin. The delta-selective antagonist, naltrindole (10 mg/kg i.p.), completely abolished the behavioural stimulation induced by 1.3 nmol/rat of DADELT II and shifted the dose-response curve to the right, without decreasing the maximum effect. The mu-preferring antagonist, naloxone, was able to antagonize the DADELT II-induced locomotor activity but only at very high doses (10 and 20 mg/kg i.p.). The i.v. administration of a large dose (10 mg/kg) of the mu 1-selective antagonist, naloxonazine, did not affect the DADELT II response. At doses up to 38 nmol/rat, the i.c.v. injection of DADELT II never induced analgesia. At doses over 20.8 nmol/rat, deltorphin always induced spontaneous controlateral barrel rotations and circling, responses which were not blocked by prior administration of naloxone or haloperidol. In studies performed on the social behaviour of rats, i.c.v. administration of 0.38 nmol/rat of DADELT II was ineffective, while 1.3 nmol/rat increased the number of social contacts. Regression analysis showed that the increase in social contacts was a primary effect of the peptide, not correlated with the increased locomotor activity.
给大鼠脑室内注射后,德尔托啡肽会诱发一种行为兴奋综合征,表现为活动增加、竖毛和嗅探。对于[D - Ala2]德尔托啡肽II(DADELT II),在0.13至3.8 nmol/大鼠的剂量范围内,活动增加和竖毛与剂量相关;对于德尔托啡肽,在1.04至20.8 nmol/大鼠的剂量范围内相关。δ选择性拮抗剂纳曲吲哚(10 mg/kg腹腔注射)可完全消除1.3 nmol/大鼠的DADELT II诱导的行为兴奋,并使剂量 - 反应曲线右移,而不降低最大效应。μ偏好性拮抗剂纳洛酮能够拮抗DADELT II诱导的活动,但仅在非常高的剂量(10和20 mg/kg腹腔注射)时有效。静脉注射大剂量(10 mg/kg)的μ1选择性拮抗剂纳洛嗪对DADELT II反应无影响。在高达38 nmol/大鼠的剂量下,脑室内注射DADELT II从未诱导出镇痛作用。在超过20.8 nmol/大鼠的剂量下,德尔托啡肽总是诱导自发的对侧桶状旋转和转圈,这些反应不会被预先给予纳洛酮或氟哌啶醇阻断。在对大鼠社会行为进行的研究中,脑室内注射0.38 nmol/大鼠的DADELT II无效,而1.3 nmol/大鼠增加了社会接触次数。回归分析表明,社会接触次数的增加是该肽的主要作用,与活动增加无关。