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MDMA‐ and METH‐induced neurotoxicity in mice: sensitization and desensitization to psychostimulants effects
Author(s) -
Ali S. F.,
Itzhak Y.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.40_11.x
Subject(s) - meth , methamphetamine , mdma , neurotoxicity , pharmacology , dopaminergic , sensitization , amphetamine , serotonergic , psychology , medicine , dopamine , chemistry , toxicity , serotonin , neuroscience , receptor , monomer , organic chemistry , acrylate , polymer
Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) and methamphetamine (METH)‐induced neurotoxicity, however, little is known about the behavioral consequences of exposure to neurotoxic doses of these substituted amphetamines. In the present study two behavioral paradigms were monitored after the exposure of mice to METH and MDMA. Swiss Webster mice were treated with METH (5 mg/kg × 3) which caused 50–65% depletion of striatal dopaminergic markers. This treatment resulted in long‐lasting sensitization to the psychomotor stimulating effect of METH (74 days after the initial exposure to METH). In the CPP paradigm, control saline pretreated mice acquired significant CPP following METH administration (0.5 mg/kg), while the METH pretreated mice acquired very low conditioned response. Following the extinction of CPP, the conditioned response to METH was completely reinstated in the control but not the METH group. The administration of MDMA (30 mg/kg × 2) resulted in 40–60% depletion of striatal and cortical dopaminergic and serotonergic markers, respectively. This treatment was associated with marked sensitization to the psychomotor stimulating effects of MDMA, METH and cocaine as determined at various intervals after the initial exposure to MDMA. These results suggest that amphetamines‐induced neurotoxicity is associated with two opposing behavioral outcomes: (1) sensitization to the psychomotor stimulating effects and (2) desensitization to the rewarding effects of related drugs. These consequences may be relevant to the psychopathology of METH and MDMA abuse. Acknowledgements: Supported by NIDA DA08584 and DA12867.