INDUCTION OF FOS PROTEIN BY 3,4-METHYLENEDIOXYMETHAMPHETAMINE (ECSTASY) IN RAT-BRAIN - REGIONAL DIFFERENCES IN PHARMACOLOGICAL MANIPULATION

Psychostimulant drugs have been reported to increase the expression of some immediate-early genes in the brain. In the present study, immuno histochemical techniques were used to assess the pattern of Fos protei n produced by 3,4-methylenedioxymethamphetamine (MDMA) in several brai n regions. Furthermore, we also studied the role of the dopamine D-1 a nd D-2 receptors and the N-methyl-D-aspartate (NMDA) receptor in the i nduction of Fos protein by MDMA. A single administration of MDMA (5, 1 0 or 20 mg/kg) caused marked induction of Fos-immunoreactivity in seve ral regions including frontal cortex, striatum and olfactory tubercle of rat brain, in a dose-dependent manner. However, in the hippocampus and cerebellum, there were few or no Fos immunoreactive cells induced by MDMA. Furthermore, the induction of Fos protein in the striatum and olfactory tubercle after administration of MDMA (10 mg/kg) was blocke d by pre-treatment with the dopamine D-1 receptor antagonist SCH 23390 (1 mg/kg) or the NMDA receptor antagonist dizocilpine (1 mg/kg), but not by the dopamine D-2 receptor antagonist (-)-sulpiride (100 mg/kg). However, the induction of Fos protein in the frontal cortex and hippo campus by MDMA was unaltered by pretreatment with SCH 23390 (1 mg/kg) or (-)-sulpiride (100 mg/kg). These results suggest that MDMA induces the expression of Fos protein in several regions of rat brain, and tha t the expression of Fos protein by MDMA in the striatum and olfactory tubercle appears to be mediated at least in part by the dopamine D-1 a nd NMDA receptors.