SPINAL ANTAGONISM OF TOLERANCE AND DEPENDENCE INDUCED BY SYSTEMICALLY ADMINISTERED MORPHINE
SPINAL ANTAGONISM OF TOLERANCE AND DEPENDENCE INDUCED BY SYSTEMICALLY ADMINISTERED MORPHINE
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DOI：
10.1016/0014-2999(83)90439-9
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发表时间：
1983-01-01
影响因子：
5
通讯作者：
TAKEMORI, AE
中科院分区：
文献类型：
--
作者：
DELANDER, GE;TAKEMORI, AE
大鼠脊髓参与吗啡耐受和依赖的形成。吗啡丸植入通过手术装配有鞘内导管的大鼠鞘内（i.t.）用盐水或2.4nmol β-氯纳曲胺（β- CNA），一种不可逆的阿片拮抗剂。24小时后，将动物皮下植入。用安慰剂或吗啡颗粒植入颗粒后72小时，评估耐受性或依赖性的发展。通过甩尾和热板镇痛试验确定，植入吗啡颗粒的对照动物对腹膜内注射吗啡诱导的镇痛产生耐受性。β-的CNA预处理拮抗了腹腔注射吗啡的作用，并阻断了吗啡植入动物耐受性的发展。通过观察几种突然戒断的特征体征来评估依赖性。用β-吗啡治疗前CNA拮抗纳洛酮诱导的戒断反应，除体重减轻外，所有体征均观察到。脊髓在阿片类药物诱导的耐受性和依赖性的形成中起着重要作用。
The spinal cord of rats was involved in development of tolerance and dependence of morphine that was administered systemically by s.c. morphine-pellet implantation. Rats, surgically fitted with intrathecal catheters, were injected intrathecally (i.t.) with saline or 2.4 nmol .beta.-chlornaltrexamine (.beta.-CNA), an irreversible opiate antagonist. Twenty-four h later, animals were implanted s.c. with either placebo or morphine pellets. Seventy-two h after implanting pellets, development of tolerance or dependence was assessed. Control animals implanted with morphine pellets became tolerant to analgesia induced by i.p. injections of morphine as determined by the use of tail flick and hot plate analgesic assays. .beta.-CNA pretreatment antagonized the effects of i.p. injections of morphine and blocked development of tolerance in morphine-implanted animals. Dependence was assessed by observing several characteristic signs of precipitated withdrawal. Treatment with .beta.-CNA before morphine treatment antagonized naloxone-induced expression of withdrawal for all signs observed except weight loss. The spinal cord evidently plays a significant role in development of tolerance and dependence induced by systemically administered opiates.