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Publication : 3,4-methylenedioxymethamphetamine self-administration is abolished in serotonin transporter knockout mice.

First Author  Trigo JM Year  2007
Journal  Biol Psychiatry Volume  62
Issue  6 Pages  669-79
PubMed ID  17306775 Mgi Jnum  J:136593
Mgi Id  MGI:3796678 Doi  10.1016/j.biopsych.2006.11.005
Citation  Trigo JM, et al. (2007) 3,4-methylenedioxymethamphetamine self-administration is abolished in serotonin transporter knockout mice. Biol Psychiatry 62(6):669-79
abstractText  BACKGROUND: The neurobiological mechanism underlying the reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA) remains unclear. The aim of the present study was to determine the contribution of the serotonin transporter (SERT) in MDMA self-administration behavior by using knockout (KO) mice deficient in SERT. METHODS: Knockout mice and wild-type (WT) littermates were trained to acquire intravenous self-administration of MDMA (0, .03, .06, .125, and .25 mg/kg/infusion) on a fixed ratio 1 (FR1) schedule of reinforcement. Additional groups of mice were trained to obtain food and water to rule out operant responding impairments. Microdialysis studies were performed to evaluate dopamine (DA) and serotonin (5-HT) extracellular levels in the nucleus accumbens (NAC) and prefrontal cortex (PFC), respectively, after acute MDMA (10 mg/kg). RESULTS: None of the MDMA doses tested maintained intravenous self-administration in KO animals, whereas WT mice acquired responding for MDMA. Acquisition of operant responding for food and water was delayed in KO mice, but no differences between genotypes were observed on the last day of training. MDMA increased DA extracellular levels to a similar extent in the NAC of WT and KO mice. Conversely, extracellular concentrations of 5-HT in the PFC were increased following MDMA only in WT mice. CONCLUSIONS: These findings provide evidence for the specific involvement of SERT in MDMA reinforcing properties.
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