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Sex-related differences in intravenous ketamine effects on dissociative stereotypy and antinociception in male and female rats
Pharmacology Biochemistry and Behavior ( IF 3.3 ) Pub Date : 2020-09-22 , DOI: 10.1016/j.pbb.2020.173042
Kennett D Radford 1 , Rina Y Berman 2 , Michael Zhang 3 , T John Wu 4 , Kwang H Choi 5
Affiliation  

Ketamine, a multimodal dissociative anesthetic drug, is widely used to treat various conditions including acute pain and treatment-resistant depression. We previously reported that subanesthetic doses of intravenous (i.v.) ketamine produced transient dissociative stereotypy and antinociception in male rats. However, sex-related differences in the effects of i.v. ketamine on these measures are not well characterized. Adult male and female Sprague-Dawley rats (10 weeks old) received an i.v. bolus saline or ketamine (2 and 5 mg/kg), and dissociative stereotypy (head weaving, ataxia, and circling) and natural behaviors (horizontal activity, rearing, and grooming) were quantified over a 10-min period. Ten minutes after the behavioral observation, antinociception was measured using a tail flick test. The i.v. ketamine administration increased head weaving, ataxia, circling, and horizontal activity while decreasing rearing and grooming behaviors in male and female rats. Following 5 mg/kg ketamine administration, ataxia was greater in female rats, while head weaving was greater in male rats. Among the female rats, head weaving was greater in the low estrogen group (diestrus phase) as compared to the high estrogen group (proestrus/estrus phase). Ketamine doses (2 and 5 mg/kg) produced antinociception in male and female rats, and female rats were more sensitive to the antinociceptive effects of 2 mg/kg ketamine. The current findings suggest that i.v. ketamine administration, a clinically relevant route of administration, may produce sex-related differences in dissociative behaviors and analgesia between males and females.



中文翻译:

静脉氯胺酮对雄性和雌性大鼠解离性刻板印象和抗伤害感受的性别相关差异

氯胺酮是一种多模式的解离性麻醉药,被广泛用于治疗各种疾病,包括急性疼痛和难治性抑郁症。我们以前曾报道过,亚麻醉剂量的静脉内(iv)氯胺酮会在雄性大鼠中产生短暂的解离性刻板印象和抗伤害感受。但是,对氯胺酮对这些措施的影响与性别有关的差异尚未得到很好的表征。成年雄性和雌性Sprague-Dawley大鼠(10周大)接受静脉推注生理盐水或氯胺酮(2和5 mg / kg),以及解离性刻板印象(头部编织,共济失调和盘旋)和自然行为(水平活动,饲养,和修饰)在10分钟内进行量化。行为观察后十分钟,使用甩尾试验测量抗伤害感受。iv 氯胺酮的施用增加了头的编织,共济失调,盘旋和水平运动,同时降低了雄性和雌性大鼠的饲养和修饰行为。氯胺酮5 mg / kg给药后,雌性大鼠共济失调更大,雄性大鼠头编织更大。在雌性大鼠中,与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。和水平活动,同时减少雄性和雌性大鼠的饲养和修饰行为。氯胺酮5 mg / kg给药后,雌性大鼠共济失调更大,雄性大鼠头编织更大。在雌性大鼠中,与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头部编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。和水平活动,同时减少雄性和雌性大鼠的饲养和修饰行为。氯胺酮5 mg / kg给药后,雌性大鼠共济失调更大,雄性大鼠头编织更大。在雌性大鼠中,与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头部编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。氯胺酮5 mg / kg给药后,雌性大鼠共济失调更大,雄性大鼠头编织更大。在雌性大鼠中,与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头部编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。服用氯胺酮5 mg / kg后,雌性大鼠的共济失调更大,雄性大鼠的头编织更大。在雌性大鼠中,与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。与高雌激素组(发情期/发情期)相比,低雌激素组(发情期)的头编织更大。氯胺酮剂量(2和5 mg / kg)在雄性和雌性大鼠中均具有镇痛作用,雌性大鼠对2 mg / kg氯胺酮的镇痛作用更为敏感。目前的发现表明,氯胺酮的静脉内给药(一种临床相关的给药途径)可能会在男性和女性之间产生与性别相关的分离行为和镇痛作用差异。

更新日期:2020-10-04
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