title: Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor.
abstract: BACKGROUND
  Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity.
  
  
  OBJECTIVE
  We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s).
  
  
  METHODS
  Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST).
  
  
  RESULTS
  After CCI injury, the neuropathic mice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline.
  
  
  CONCLUSIONS
  Curcumin can normalize the depressive-like behaviors of neuropathic mice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.
authors.affiliation: Department of Pharmacology, School of Medical Science, Ningbo University, Ningbo, Zhejiang Province, 315211, China, zhaoxin@nbu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.forename: Jun-Fang
authors.initials: JF
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020422:Mononeuropathies / Q000150:complications* / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming
chemical_list: D011963:Receptors, GABA-A; D012701:Serotonin; D003474:Curcumin