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Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit morphine's rewarding effect in rats

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Abstract

Rationale

Recent animal studies reported that curcumin, the active constituent of Curcuma longa, has several central actions and may attenuate morphine tolerance.

Objectives

In the present study, we utilized the intracranial self-stimulation (ICSS) paradigm to examine the effects of the commercially available curcuminoid mixture and each one of its components, individually, on brain stimulation reward and on the reward-facilitating effect of morphine.

Methods

Male Sprague-Dawley rats were implanted with an electrode into the medial forebrain bundle and trained to respond for electrical stimulation using a rate-frequency paradigm. In the first study, rats were injected with graded doses either of the curcuminoid mixture, or curcumin I, or II, or III. In the second study, we examined whether a low dose of the curcuminoid mixture or each individual curcumin analogue composing it could counteract the reward-facilitating effect of morphine.

Results

At low doses, both the curcuminoid mixture and curcumin I did not affect brain stimulation reward, whereas, higher doses increased ICSS thresholds. Curcumin II and curcumin III did not affect brain stimulation reward at any doses. Subthreshold doses of the curcuminoid mixture and curcumin I inhibited the reward-facilitating effect of morphine.

Conclusion

Both the curcuminoid mixture and curcumin I lack hedonic properties and moderate the reward-facilitating effect of morphine. Our data suggest that curcumin interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids and provide evidence that curcumin may be a promising adjuvant for attenuating morphine’s rewarding effects in patients who are under long-term opioid therapy.

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Acknowledgments

The authors would like to specially thank Prof. G. Paxinos for his kind financial support. This study was also supported by the Department of Psychology of the University of Crete. Acknowledgements also to the City Unity College, Department of Psychology, Athens, Greece for facilitating this collaboration. The experiments reported comply with the European Community Council Directive (86/609/EEC).

Conflict of interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, 74100, Rethymno, Crete, Greece

    Vicky Katsidoni, Marilena Fotiadou & George Panagis

  2. National Centre for Scientific Research “Demokritos”, Institute of Biosciences and Applications, 15310, Ag. Paraskevi, Attiki, Athens, Greece

    Polyxeni Alexiou, Maria Pelecanou & Marina Sagnou

Authors
  1. Vicky Katsidoni
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  2. Polyxeni Alexiou
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  3. Marilena Fotiadou
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  4. Maria Pelecanou
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  5. Marina Sagnou
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  6. George Panagis
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Correspondence to George Panagis.

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Katsidoni, V., Alexiou, P., Fotiadou, M. et al. Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit morphine's rewarding effect in rats. Psychopharmacology 231, 4467–4478 (2014). https://doi.org/10.1007/s00213-014-3603-5

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  • DOI: https://doi.org/10.1007/s00213-014-3603-5

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