Reduction of in vivo binding of [3H]paroxetine in mouse brain by 3,4-methylenedioxymethamphetamine.
Kenji Hashimoto, Tsuyoshi Goromaru
Neuropharmacology July 1990 DOI: 10.1016/0028-3908(90)90024-l (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | MDMA |
| Dose | 15 mg/kg, i.p. |
| Topics | MDMA |
| Key findings | MDMA pretreatment (15 mg/kg, i.p., 3 hours before) significantly decreased in vivo binding of [3H]paroxetine to serotonin uptake sites in mouse hypothalamus and cerebral cortex in a dose-dependent manner, while in vitro binding to brain membranes was not altered. The authors discuss this in vivo versus in vitro discrepancy. |
Abstract
The effects of 3,4-methylenedioxymethamphetamine (MDMA) on the in vivo binding of [3H]paroxetine, a potent and selective 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor, in the brain of the mouse were studied. The distribution of radioactivity in the brain of the mouse, after intravenous administration of [3H]paroxetine, was significantly altered by pretreatment with MDMA (15 mg/kg, i.p., 3 hr before). The hypothalamus/cerebellum and cerebral cortex/cerebellum ratios, as a function of time, were significantly decreased after the pretreatment with MDMA, indicating that the in vivo binding of [3H]paroxetine to uptake sites for 5-HT in the brain of the mouse was significantly decreased by MDMA. These ratios could reflect those of the total binding, to the non-specific binding and free ligand, since the cerebellum has very low levels of binding for [3H]paroxetine. Furthermore, these ratios decreased after pretreatment with MDMA, in a dose-dependent manner. However, the binding of [3H]paroxetine to membranes from the brain of the mouse in vitro was not altered by treatment with MDMA. The discrepancy between the in vivo binding and in vitro binding of [3H]paroxetine in the brain of the mouse is discussed.