MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter binding.
3,4-Methylenedioxymethamphetamine (MDMA) self-administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug-naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self-administration was measured during daily 6-h sessions. Dose-effect data were obtained for MDMA (0.25-1.0 mg/kg/infusion) self-administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter- or self-administered MDMA on [3H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self-administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self-administration during the 15-day test period. The percentage of rats that acquired MDMA self-administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self-administration, and cocaine self-administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self-administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter-administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long-term self-administration may lead to long-lasting deficits in serotonin neurotransmission.
Schenk
Susan
S
Victoria University of Wellington, School of Psychology, Wellington, New Zealand. Susan.Schenk@vuw.ac.nz
Hely
Lincoln
L
Lake
Barbara
B
Daniela
Evangelene
E
Gittings
David
D
Mash
Deborah C
DC
D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D017374:Paroxetine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods; D018490:Serotonin Agents / Q000008:administration & dosage*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D014316:Tritium; D017374:Paroxetine; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine