Effects of Monoamine Reuptake Inhibitors in Assays of Acute Pain-Stimulated and Pain-Depressed Behavior in Rats

被引:52
|
作者
Rosenberg, Marisa B. [1 ]
Carroll, F. Ivy [2 ]
Negus, S. Stevens [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA
[2] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA
来源
JOURNAL OF PAIN | 2013年 / 14卷 / 03期
关键词
Analgesia; antidepressant; dopamine; intracranial self-stimulation; monoamine reuptake inhibitor; INTRACRANIAL SELF-STIMULATION; DOPAMINE TRANSPORTERS; PERSISTENT PAIN; ANIMAL-MODELS; ANTIDEPRESSANTS; SEROTONIN; RADIOLIGAND; ANALGESICS; COCAINE; NOREPINEPHRINE;
D O I
10.1016/j.jpain.2012.11.006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Pain is associated with stimulation of some behaviors (eg, withdrawal reflexes) but depression of many other behaviors (eg, feeding, locomotion, positively reinforced operant behavior). Drugs that block reuptake of serotonin, norepinephrine, and/or dopamine are widely used to treat depression, and they have also emerged as useful drugs for treatment of pain. This study compared effects of selective and mixed-action inhibitors of serotonin, norepinephrine, and/or dopamine reuptake in assays of acute pain-stimulated and pain-depressed behavior. Intraperitoneal injection of dilute acid served as a noxious stimulus to stimulate a writhing response or depress intracranial self-stimulation (ICSS) in Sprague Dawley rats. Selective reuptake inhibitors of serotonin (citalopram, clomipramine) and norepinephrine (nisoxetine, nortriptyline) and a mixed-action reuptake inhibitor of serotonin and norepinephrine (milnacipran) blocked acid-stimulated writhing but failed to block acid-induced depression of ICSS. Selective dopamine reuptake inhibitors (RTI-113 [3 beta-(4-chlorophenyl)tropane-2 beta-carboxylic acid phenyl ester hydrochloride], bupropion) and a triple reuptake inhibitor of dopamine, serotonin, and norepinephrine (RTI-112 [3 beta-(3-methyl-4-chlorophenyl) tropane-2 beta-carboxylic acid methyl ester hydrochloride]) blocked both acid-stimulated writhing and acid-induced depression of ICSS, although these drugs also produced an abuse-related facilitation of ICSS in the absence of the noxious stimulus. These results support further consideration of dopamine reuptake inhibitors as candidate analgesics, although abuse liability remains a concern. Perspective: Monoamine reuptake inhibitors are used to treat depression and some forms of pain. This study examined effects of monoamine reuptake inhibitors in a predinical assay of pain-related behavioral depression. The results support further consideration of dopamine reuptake inhibitors as candidate analgesics under selected circumstances, although abuse liability remains a concern. (C) 2013 by the American Pain Society
引用
收藏
页码:246 / 259
页数:14
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