Differential regulation by stimulants of neocortical expression of mrt1, arc, and homer1a mRNA in the rats treated with repeated methamphetamine.

The present work was conducted to obtain clues for the possible roles of a novel stimulant-inducible gene mrt1 (methamphetamine-responsive transcript 1) encoding a PDZ-PX protein in stimulant-induced behavioral sensitization. In the young adult rats, repeated daily treatment with methamphetamine (4 mg/kg, intraperitoneally, once a day) for 5 days caused an enhanced behavioral response to methamphetamine: behavioral sensitization. The 5-day intermittent administration of MAP upregulated the basal expression of mrt1 transcripts and eliminated the increasing effects of a challenge dose of MAP (1.6 mg/kg, i.p.) or cocaine (30 mg/kg, i.p.) on mrt1 expression on day 14 of withdrawal in the neocortex that has been considered to be composed of a neuron circuit implicated in the sensitization phenomenon. In contrast, the basal expression of other stimulant-inducible and plasticity-related genes arc and homer1a and the ability of MAP or cocaine challenge to augment the amounts of their transcripts were not affected by the repeated MAP regimen in the cortical area. These findings suggest the differential regulation by stimulant of neocortical mrt1, arc, and homer1a expression in the behaviorally sensitized animals and supports the view that stimulant induction of mrt1 may be involved in the early molecular signalings for stimulant sensitization. Copyright 2003 Wiley-Liss, Inc.