Apr 10, 2003

Different glial response to methamphetamine- and methylenedioxymethamphetamine-induced neurotoxicity

Naunyn-Schmiedeberg's Archives of Pharmacology
David PubillElena Escubedo

Abstract

The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an amphetamine derivative with specific action on the serotonergic system) were compared with those of methamphetamine (a derivative with specific action on dopaminergic system) in rats. Both drugs induced a very similar loss of body weight, especially evident 24 h after treatment. Their hyperthermic profile was also very similar and was dependent on ambient temperature, corroborating the thermo-dysregulatory effect of both substances. Methamphetamine (four injections of 10 mg kg(-1) s.c. at 2-h intervals) induced the loss of dopaminergic (35%) but not of serotonergic, terminals in the rat striatum and, simultaneously, a significant increase in striatal peripheral-type benzodiazepine receptor density, pointing to a glial reaction. Evidence for this drug-induced astrogliosis was the increased heat shock protein 27 (HSP27) expression in striatum, cortex and hippocampus. MDMA (20 mg kg(-1) s.c. b.i.d. for 4 days) induced a similar dopaminergic lesion in the striatum 3 days post-treatment, which reversed 4 days later. An important neurotoxic effect on serotonergic terminals was also observed in the cortex, striatum and hippocampus 3 days p...Continue Reading

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Mentioned in this Paper

HSPB1 gene
Heat shock proteins
Amphetamine
Cortex Bone Disorders
Adrenal Cortex Diseases
Immunoreactivity
Glial Fibrillary Acidic Protein
Neostriatum
Hsp27
Serotonin-binding protein

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