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.