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Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats

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Abstract

Rationale

Melatonin is a hormone involved in the entrainment of circadian rhythms, which appears dysregulated in drug users. Further, it has been demonstrated that melatonin can modulate the reinforcing effects of several drugs of abuse and may therefore play a role in drug addiction.

Objective

Here, we investigated whether administration of melatonin reduces relapse-like behavior and the motivation to seek cocaine in rats.

Methods

Male Sprague-Dawley rats were submitted to long-term cocaine self-administration training. Thereafter, melatonin effects were assessed on: (1) the motivation to work for cocaine in the break point test, (2) the relapse-like behavior in the cue-induced reinstatement test, (3) the distance traveled in the open field test, and (4) sucrose preference in a two-bottle choice paradigm. Melatonin, 25 or 50 mg/kg, was injected 3–4 h after the dark phase onset, 30 min prior to each test.

Results

Both doses of melatonin decreased the number of active pokes in both break point and cue-induced reinstatement tests, demonstrating that melatonin can reduce the cocaine-seeking behavior and the motivation to work for cocaine. Administration of the higher dose of this hormone, however, significantly reduced the number of inactive pokes during the cue-induced reinstatement test and tended to reduce animals’ locomotor activity in the open field test. Sucrose preference was unchanged in both vehicle- and melatonin-treated animal groups.

Conclusions

Our data suggest that melatonin administration may lower the risk of relapse triggered by cues in cocaine-experienced animals.

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Acknowledgements

We would like to thank Elena Büchler for her technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) Reinhart-Koselleck Award SP 383/5-1; and the ERANET COCADDICT. TTT was funded by CAPES Foundation, Ministry of Education of Brazil, Brasília—DF 70040-020, Brazil.

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Authors and Affiliations

  1. Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany

    Tatiane T. Takahashi, Valentina Vengeliene & Rainer Spanagel

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  1. Tatiane T. Takahashi
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  2. Valentina Vengeliene
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  3. Rainer Spanagel
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Correspondence to Rainer Spanagel.

Ethics declarations

All experimental procedures were approved by the Committee on Animal Care and Use (Regierungspräsidium Karlsruhe), and carried out in accordance with the local Animal Welfare Act and the European Communities Council Directive of 24 November 1986 (86/609/EEC).

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The authors declare that they have no conflict of interest.

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Takahashi, T.T., Vengeliene, V. & Spanagel, R. Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats. Psychopharmacology 234, 1741–1748 (2017). https://doi.org/10.1007/s00213-017-4576-y

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