MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter binding

被引:57
作者
Schenk, Susan [1 ]
Hely, Lincoln
Lake, Barbara
Daniela, Evangelene
Gittings, David
Mash, Deborah C.
机构
[1] Victoria Univ Wellington, Sch Psychol, Wellington, New Zealand
[2] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33152 USA
关键词
drug reinforcement; MDMA abuse; neuroadaptation;
D O I
10.1111/j.1460-9568.2007.05932.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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-naive 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 [(3)H] 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.
引用
收藏
页码:3229 / 3236
页数:8
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