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Mdma and Methamphetamine: An Investigation of a Neurochemical and Behavioral Cross-Tolerance in the Rat

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dc.contributor.advisorJerrold S Meyer
dc.contributor.authorHenderson, Christina S
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.contributor.departmentNeuroscience & Behavior
dc.date2023-09-22T19:59:06.000
dc.date.accessioned2024-04-26T21:08:34Z
dc.date.available2009-10-31T00:00:00Z
dc.date.issued2009-01-01
dc.date.submitted2009-May
dc.description.abstractWe previously found that intermittent administration of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) to adolescent male rats protected against the behavioral and serotonergic neurotoxic effects of a subsequent MDMA binge. Similar results have been reported for the dopamine (DA) neurotoxin methamphetamine (METH). The present study tested the hypothesis that intermittent adolescent MDMA exposure would protect against the DA neurotoxic effects of a METH binge. Male Sprague-Dawley rats were injected s.c. with MDMA (10 mg/kg x 2; 4-h interdose interval) or saline every fifth day from postnatal day (PD) 35 through PD 60. The animals were then challenged with either a low- or high-dose METH binge (4 or 8 mg/kg x 4; 2- h interdose interval) or saline on PD 67. Activity was measured 1 day after the binge, and regional serotonin transporter (SERT) and dopamine transporter (DAT) expression were analyzed at PD 74 by radioligand binding. All animals treated with METH on the challenge day became hyperthermic, independent of pretreatment conditions. Both MDMA-pretreated and drug-naïve rats also showed a dose-dependent hypoactivity 24 h after the first dose of the METH binge. The SERT binding results indicated that adolescent pretreatment with MDMA provided full or partial protection (depending on the brain region) against the serotonergic deficits produced by METH in previously drug-naïve animals. In contrast, MDMA pretreatment failed to protect against METH-induced decreases in striatal DAT binding. These results suggest that the neuroprotective 2 effects of adolescent MDMA pretreatment are confined to the serotonergic system, possibly reflecting a selective upregulation of antioxidant mechanisms in that system.
dc.description.degreeMaster of Science (M.S.)
dc.identifier.doihttps://doi.org/10.7275/835043
dc.identifier.urihttps://hdl.handle.net/20.500.14394/47249
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1351&context=theses&unstamped=1
dc.source.statuspublished
dc.subjectPharmacology
dc.subjectMDMA
dc.subjectMethamphetamine
dc.subjectRats
dc.subjectCross-tolerace
dc.subjectSERT
dc.subjectDAT
dc.subjectBehavioral Neurobiology
dc.subjectMolecular and Cellular Neuroscience
dc.titleMdma and Methamphetamine: An Investigation of a Neurochemical and Behavioral Cross-Tolerance in the Rat
dc.typecampus
dc.typearticle
dc.typethesis
digcom.contributor.authorisAuthorOfPublication|email:chenders@nsm.umass.edu|institution:University of Massachusetts Amherst|Henderson, Christina S
digcom.date.embargo2009-10-31T00:00:00-07:00
digcom.identifiertheses/371
digcom.identifier.contextkey835043
digcom.identifier.submissionpaththeses/371
dspace.entity.typePublication
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