Methamphetamine‐Induced Locomotor Sensitization in C57BL/6 Mice Requires the MT1 Melatonin Receptor

Abstract

Genetic deletion of both MT1 and MT2 melatonin receptors abrogates the development and expression of locomotor sensitization in melatonin proficient C3H/HeN mice repeatedly pretreated with methamphetamine (METH) (Hutchinson et al., Program 669.12. 2010 Neuroscience Meeting Planner). However, C57BL/6 mice deficient in pineal melatonin do not develop or express sensitization using the same METH treatment paradigm. Here we assessed the role of MT1 melatonin receptors in locomotor sensitization using a two METH injection protocol. Mice were pretreated with either vehicle or METH (1.2 mg/kg, i.p.) on Day 1, then challenged on Day 8 with METH (1.2 mg/kg, i.p.). On Day 1 METH increased locomotor activity in both WT [60.6±5.5 meters traveled (n=12), p<0.05] and MT1KO mice [57.1±6.5 m (n=12), p<0.05] when compared to vehicle‐treated controls [15.6±4.4 m (n=12), 11.9±1.5 m (n=12) respectively]. METH challenge triggered a sensitized response in METH‐pretreated WT mice [106.0±5.2 m (n=12), p<0.05], but not in METH‐pretreated MT1KO mice [57.1±6.5 (n=12), p>0.05] compared to corresponding vehicle‐pretreated controls [63.2±7.5 m (n=12), 53.1±5.0 m (n=12) respectively]. Our results indicate that in C57BL/6 mice, the expression of the MT1 receptor is required for the induction of METH‐induced sensitization after a single METH pretreatment. Supported by DA021870 to MLD.