title: A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats.
abstract: BACKGROUND
  Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its antinociceptive properties.
  
  
  METHODS
  The authors examined whether the spared nerve injury model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats spared nerve injury-induced depression.
  
  
  RESULTS
  Spared nerve injury-treated rats, compared with control rats, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10 mg/kg) did not alter spared nerve injury-induced hypersensitivity; however, it treated spared nerve injury-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control rats 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control rats 5 days after administration).
  
  
  CONCLUSIONS
  Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain.
authors.affiliation: Department of Anesthesiology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yossef
authors.initials: Y
authors.lastname: Goffer
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.forename: David S
authors.initials: DS
authors.lastname: Tukey
authors.forename: D B
authors.initials: DB
authors.lastname: Shamir
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Eberle
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Zou
authors.forename: Thomas J J
authors.initials: TJ
authors.lastname: Blanck
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents; D001522:Behavior, Animal / Q000187:drug effects; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000209:etiology* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000523:psychology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009437:Neuralgia / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose; D013550:Swimming / Q000523:psychology; D013649:Taste / Q000187:drug effects
chemical_list: D000778:Anesthetics, Dissociative; D000928:Antidepressive Agents; D013395:Sucrose; D007649:Ketamine; D003345:Corticosterone