title: Effects of monoamine reuptake inhibitors in assays of acute pain-stimulated and pain-depressed behavior in rats.
abstract: 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 [3ß-(4-chlorophenyl)tropane-2ß-carboxylic acid phenyl ester hydrochloride], bupropion) and a triple reuptake inhibitor of dopamine, serotonin, and norepinephrine (RTI-112 [3ß-(3-methyl-4-chlorophenyl)tropane-2ß-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.
  
  
  CONCLUSIONS
  Monoamine reuptake inhibitors are used to treat depression and some forms of pain. This study examined effects of monoamine reuptake inhibitors in a preclinical 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.
authors: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
authors: Marisa B
authors: MB
authors: Rosenberg
authors: F Ivy
authors: FI
authors: Carroll
authors: S Stevens
authors: SS
authors: Negus
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism; D001703:Biophysics; D003216:Conditioning, Operant; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004558:Electric Stimulation; D019344:Lactic Acid / Q000009:adverse effects; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000150:complications* / Q000523:psychology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012653:Self Stimulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D014179:Neurotransmitter Uptake Inhibitors; D019344:Lactic Acid