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Physiol Behav. 2014 Jun 10;132:79-86. doi: 10.1016/j.physbeh.2014.04.049. Epub 2014 May 9.

Genetic deletion of the MT1 or MT2 melatonin receptors abrogates methamphetamine-induced reward in C3H/HeN mice.

Author information

1
Department of Pharmacology & Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, United States.
2
Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, United States.
3
Department of Pharmacology & Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, United States. Electronic address: mdubo@buffalo.edu.

Abstract

The drug of abuse methamphetamine (METH) is known for its ability to enhance reward responses. The rewarding properties of psychostimulants have been shown to vary across time of day in mice. The goal of this study was to determine the role of the MT1 and MT2 melatonin receptors in METH-induced reward, as measured by the conditioned place preference (CPP) paradigm during the light and dark phases. C3H/HeN wild-type mice were trained for METH-induced CPP at either ZT 6-8 (ZT: Zeitgeber time; ZT 0=lights on), when endogenous melatonin levels are low, or ZT 19-21, when melatonin levels are high. These time points also correspond to the high and low points for expression of the circadian gene Period1, respectively. The locomotor response to METH (1.2mg/kg, ip) treatment was of similar magnitude at both times; however only C3H/HeN mice conditioned to METH at ZT 6-8 developed a place preference. C3H/HeN mice with a genetic deletion of either the MT1 (MT1KO) or MT2 (MT2KO) receptor tested at ZT 6-8 or ZT 19-21 did not develop a place preference for METH, though both showed a similar increase in locomotor activity following METH treatment when compared to wild-type mice. We conclude that in our mouse model METH-induced CPP is dependent on time of day and the presence of the MT1 or MT2 receptors, suggesting a role for melatonin in METH-induced reward.

KEYWORDS:

C3H/HeN mouse; Conditioned place preference; MT(1) or MT(2) knockout mice; Melatonin; Melatonin receptors

PMID:
24813704
PMCID:
PMC4698795
DOI:
10.1016/j.physbeh.2014.04.049
[Indexed for MEDLINE]
Free PMC Article

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