A reliable model of intravenous MDMA self-administration in naïve mice.
BACKGROUND
MDMA is one of the most widely consumed recreational drugs in Europe. However, the mechanisms involved in the reinforcing properties of MDMA are still unclear. In this sense, the establishment of a reliable model of MDMA self-administration in mice could represent an important approach to study the neuronal substrates associated with MDMA reward by using genetically modified mice.


OBJECTIVE
To develop a reliable model of operant intravenous MDMA self-administration in drug-naïve mice.


METHODS
Mice were trained to acquire intravenous self-administration of MDMA at different doses (0, 0.06, 0.125, 0.25, 0.5 and 1.0 mg/kg/infusion) on a FR1 schedule of reinforcement for 15 consecutive days. The motivational value of different doses of MDMA (0.125, 0.25 and 0.5 mg/kg/infusion) was then tested using a progressive ratio paradigm. Finally, [3H]-mazindol autoradiographic studies were carried out in order to quantitatively assess presynaptic dopamine transporter (DAT) binding sites in the striatum of mice trained to self-administer MDMA (0 and 1.0 mg/kg/infusion) during 15 days.


RESULTS
The latency for discrimination between the active and inactive holes, as well as the number of animals acquiring stability criteria, varied as a function of the dose of MDMA. The mice responding for intermediate doses (0.125, 0.25 and 0.5 mg/kg/infusion) discriminated earlier than those responding for low (0.06 mg/kg/infusion) or high (1.0 mg/kg/infusion) doses. The percentage of animals achieving stability criteria increased with days of testing and was inversely proportional to the dose of MDMA. The breaking points achieved for doses of 0.125 and 0.25 mg/kg/infusion were significantly higher than for a dose of 0.5 mg/kg/infusion. No significant DAT neurotoxicity was observed in the striatum of animals self-administering MDMA at a dose of 1 mg/kg/infusion.


CONCLUSIONS
The present results show that MDMA can be reliably self-administered by drug-naïve mice.
Trigo
José Manuel
JM
Universitat Pompeu Fabra, Calle Dr. Aiguader, 80, 08003, Barcelona, Spain.
Panayi
Fany
F
Soria
Guadalupe
G
Maldonado
Rafael
R
Robledo
Patricia
P
D000818:Animals; D001345:Autoradiography; D003216:Conditioning, Operant / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008454:Mazindol; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D012055:Reinforcement Schedule; D012646:Self Administration; D019966:Substance-Related Disorders / Q000523:psychology*
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D006213:Hallucinogens; D008454:Mazindol; D018817:N-Methyl-3,4-methylenedioxyamphetamine