title: (±)3,4-methylenedioxymethamphetamine ("ecstasy") treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain.
abstract: (±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment.
authors.affiliation: Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hemmerle
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Dickerson
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Herring
authors.forename: Tori L
authors.initials: TL
authors.lastname: Schaefer
authors.forename: Charles V
authors.initials: CV
authors.lastname: Vorhees
authors.forename: Michael T
authors.initials: MT
authors.lastname: Williams
authors.forename: Kim B
authors.initials: KB
authors.lastname: Seroogy
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; D020933:Neurotrophin 3; D012333:RNA, Messenger; D018490:Serotonin Agents; D014446:Tyrosine 3-Monooxygenase; D020813:Receptor, trkB; D020812:Receptor, trkC; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003345:Corticosterone