Abstract
1308
Introduction: The misuse of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) has drawn a growing concern worldwide for its psychophysiological impacts on humans. Among the acute symptoms of MDMA administration, hyperthermia is one of the important causes leading to the death of the abusers. Although MDMA-induced hyperthermia has been previously shown to be associated with uncoupling proteins of brown adipose tissue, mechanisms underlying this effect are still poorly understood. Brown adipose tissue (BAT) is especially abundant in the newborns and hibernating mammals and plays a key role in maintenance of a stable body temperature via heat generation. Glucose is required as an energy source in the process of thermogenesis which is regulated by thyroid hormones. To the best of our knowledge, there is no study revealing the relationships among thyroid hormones, brown adipose tissue and MDMA. We will use positron emission tomography (PET) with [18F]-FDG (an analog of glucose) to evaluate the activity of BAT in the rats. In addition, MDMA-induced long-term serotonergic neurotoxicity has been shown to be associated with a decrease in serotonin transporter (SERT) density and depressive-like behaviors. Hence, we will also explore the serotonergic toxicity and depressive-like behaviors by 4-[18F]-ADAM (a specific radioligand for serotonin transporters) PET imaging and forced swim test, respectively. In this study, [18F]-FDG PET imaging showed that methimazole, an antithyroid drug, could provide protective effects against MDMA-induced hyperthermia by decreasing the activation of cervical and interscapular BAT. 4-[18F]-ADAM PET imaging also revealed that methimazole protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus. The PET data were comparable to the observation from the forced swim test that methimazole sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that methimazole prevent the acute hyperthermia and protect against neurobiological and depressive-like behavioral changes induced by MDMA.
In this issue
Jump to section
Related Articles
Cited By...
- No citing articles found.