title: Induction of Fos protein by 3,4- methylenedioxymethamphetamine (Ecstasy) in rat brain: regional differences in pharmacological manipulation.
abstract: Psychostimulant drugs have been reported to increase the expression of some immediate-early genes in the brain. In the present study, immunohistochemical techniques were used to assess the pattern of Fos protein produced by 3,4-methylenedioxymethamphetamine (MDMA) in several brain regions. Furthermore, we also studied the role of the dopamine D and D receptors and the N-methyl- D-aspartate (NMDA) receptor in the induction of Fos protein by MDMA. A single administration of MDMA (5, 10 or 20 mg/kg) caused marked induction of Fos-immunoreactivity in several 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 blocked by pre-treatment with the dopamine D receptor antagonist SCH 23390 (1 mg/kg) or the NMDA receptor antagonist dizocilpine (1 mg/kg), but not by the dopamine D receptor antagonist (-)-sulpiride (100 mg/kg). However, the induction of Fos protein in the frontal cortex and hippocampus 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 that 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 and NMDA receptors.
authors.affiliation: Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Tomitaka
authors.affiliation: Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Narita
authors.affiliation: Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Minabe
authors.affiliation: Division of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo.Division of Drug Dependence and Psychotropic Drug Clinical Research, National Institute of Mental Health, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Iyo