Age-dependent sensitivity of rats to the long-term effects of the serotonergic neurotoxicant (+/-)-3,4-methylenedioxymethamphetamine (MDMA) correlates with the magnitude of the MDMA-induced thermal response.
H W Broening, John F Bowyer, William Slikker
Journal of Pharmacology and Experimental Therapeutics October 1, 1995 DOI: 10.1016/s0022-3565(25)12053-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats at postnatal days 10, 40, and 70 |
| Intervention | MDMA |
| Duration | 1 week after MDMA administration |
| Topics | MDMA Serotonin |
| Keywords | Hyperthermia Hypothermia Serotonin reuptake inhibitor Pharmacology Neurotoxicity Endocrinology Anesthesia |
| Citations | 151 |
| Key findings | Hyperthermia is necessary for MDMA to cause long-term reductions in serotonin content and reuptake sites in the frontal cortex of rats. |
Abstract
The effects of developmental age on (+/-)-3,4-methylenedioxymethamphetamine (MDMA)-induced reductions in 5-hydroxytryptamine (5-HT) content and 5-HT reuptake sites were investigated in conjunction with the effects of developmental age on MDMA-induced thermoregulatory responses. MDMA was administered to rats at postnatal days (PND) 10, 40 and 70 in a range of ambient temperature environments (10 degrees C, 25 degrees C and 33 degrees C). Animals were monitored for alterations in body temperature and sacrificed 1 week after MDMA administration. MDMA administration at PND 10 did not result in persistent reductions in 5-HT content or 5-HT reuptake sites in frontal cortex, nor could a hyperthermic response be elicited. In contrast, MDMA administration at PND 40 and PND 70 resulted in a hypothermic response in cold environments (10 degrees C) and a hyperthermic response in warm environments (> or = 25 degrees C). When hypothermia was observed after MDMA (10 degrees C environment), long-term reductions in 5-HT content and 5-HT reuptake sites were significantly attenuated or abolished. Conversely, when a hyperthermic response was observed (25 degrees C and 33 degrees C environments), long-term MDMA-induced reductions in 5-HT content and 5-HT reuptake sites were significantly enhanced. Thus, thermal responses significantly correlated with MDMA-induced reductions in 5-HT content and 5-HT reuptake sites. These experiments demonstrate a role for hyperthermia in the expression of serotonergic neurotoxicity after MDMA administration.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 59
- Amphetamine toxicities Annals of the New York Academy of Sciences January 8, 2010
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- 3,4-Methylenedioxymethamphetamine (Ecstasy)-Induced Learning and Memory Impairments Depend on the Age of Exposure during Early Development Journal of Neuroscience May 1, 2001
- The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives British Journal of Pharmacology March 3, 2010
- Studies on the role of dopamine in the degeneration of 5‐HT nerve endings in the brain of Dark Agouti rats following 3,4‐methylenedioxymethamphetamine (MDMA or ‘ecstasy’) administration British Journal of Pharmacology February 1, 1999
and 54 more in the library