title: Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in the rat brain: an autoradiography study.
abstract: Previous studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce a heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated male Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and sacrificed them the day after to perform [(125)I]Epibatidine binding autoradiograms on serial coronal slices. MDMA induced significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory, motor, auditory and retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 34% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The heteromeric nAChR up-regulation in certain areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term consumption of MDMA.
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ciudad-Roberts
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Camarasa
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain. Electronic address: d.pubill@ub.edu.
authors.forename: David
authors.initials: D
authors.lastname: Pubill
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), Institute of Biomedicine (IBUB), Faculty of Pharmacy, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Escubedo
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D004347:Drug Interactions; D006213:Hallucinogens / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000493:pharmacokinetics; D017374:Paroxetine / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics; D011859:Radiography; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D014316:Tritium / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D006213:Hallucinogens; D007457:Iodine Radioisotopes; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D018722:Nicotinic Agonists; D017374:Paroxetine; D011725:Pyridines; D011978:Receptors, Nicotinic; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; C082748:epibatidine
keywords: Epibatidine; MDMA; Nicotine; Nicotinic receptor; Up-regulation