MDMA induces Per1, Per2 and c-fos gene expression in rat suprachiasmatic nuclei

RATIONALE: ±3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a psychoactive drug that has marked effects on the serotonergic system. Serotonergic agonists are known to interact with the circadian pacemaker located in the suprachiasmatic nuclei (SCN). OBJECTIVES: Given changes reported in the behavioral activity rhythm followingMDMAtreatment, the effects ofMDMAon core clock gene (Per1, Per2) and c-fos expression were evaluated. METHODS: Male Long–Evans rats (n=72) were injected once with MDMA (5 mg/kg i.p.) or saline either at the middle of their ‘rest’ phase (Zeitgeber Time: ZT6) or the middle of their ‘active’ phase (Zeitgeber Time: ZT16) and killed at 30, 60, or 120 min posttreatment for gene expression analysis in the SCN using PCR. Behavioral rhythms of a separate group of rats (n=20) were measured following treatment at ZT16 while they were held in constant darkness for 10 days posttreatment. RESULTS: At ZT6, c-fos mRNA was significantly induced 120 min post-MDMA treatment but there were no significant changes in Per1 or Per2 mRNA expression. At ZT16, there were significant inductions of c-fos mRNA (30 and 60 min) and Per1 and Per2 mRNA (both 60 min) post-MDMA treatment. However, no differences in behavioral activity patterns were noted following MDMA treatment at ZT16. CONCLUSIONS: These data provide evidence that MDMA has time of day dependent actions on SCN functioning, as evident from its induction of core clock genes that are important for generating and maintaining circadian rhythmicity.Rowan P. Ogeil, David J. Kennaway, Mark D. Salkeld, Shantha M.W. Rajaratnam and Jillian H. Broadbea