Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor

Abstract

Rationale

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.

Conclusion

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.

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Acknowledgments

This work was supported by the K.C. Wong Magna Fund in Ningbo University, National Natural Science Foundation of China (81201050), Natural Science Foundation of Zhejiang Province (LY12H09002), and Innovative Research Team of Ningbo (2009B21002).

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The authors declare no conflicts of interest.

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Correspondence to Xin Zhao.

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Zhao, X., Wang, C., Zhang, JF. et al. Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor. Psychopharmacology 231, 2171–2187 (2014). https://doi.org/10.1007/s00213-013-3368-2

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Keywords

  • Curcumin
  • Depression
  • Neuropathic pain
  • Serotonin
  • GABAA