Augmentation of serotonin release by sustained exposure to MDMA and methamphetamine in rat organotypic mesencephalic slice cultures containing raphe serotonergic neurons.
Megumi Higuchi, Yuichi Suzuki, Yumi Yatani, Yutaka Kitagawa, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
Journal of Neurochemistry September 2008 DOI: 10.1111/j.1471-4159.2008.05583.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat organotypic mesencephalic slice cultures containing the raphe nuclei |
| Interventions | 3 4-methylenedioxymethamphetamine (MDMA) methamphetamine (METH) MK-801 |
| Dose | MDMA and METH 1-1000 microM for 4 days; MDMA challenge 10 microM; MK-801 10 microM |
| Duration | 4-day exposure, 1-day withdrawal, then challenge |
| Measures | tryptophan hydroxylase (TPH) immunostaining, serotonin tissue content, [(3)H]citalopram binding, serotonin release |
| Topics | MDMA Serotonin |
| Key findings | Sustained exposure of rat mesencephalic slice cultures to MDMA or methamphetamine induced serotonergic sensitization, shown by augmented serotonin release after a drug challenge, without evidence of serotonergic neurotoxicity. The NMDA receptor antagonist MK-801 attenuated the development of MDMA-induced sensitization, suggesting the effect depends on NMDA receptor activation. |
Abstract
Several lines of evidence suggest the involvement of the raphe-serotonergic neurons in addiction to psychostimulants and some recreational drugs. In this study, we established rat organotypic mesencephalic slice cultures containing the raphe nuclei and examined the effects of sustained exposure to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH). Immunostaining for tryptophan hydroxylase (TPH) studies revealed that serotonergic neurons were abundant in the slice cultures. Sustained exposure to MDMA and METH (1-1000 microM) for 4 days had little effect on the serotonin tissue content, [(3)H]citalopram binding, or expression/phosphorylation of TPH. Treatment with MDMA or METH for 30 min increased serotonin release in a concentration-dependent manner. Slice cultures were exposed to MDMA for 4 days following a 1-day withdrawal period and then challenged with MDMA (10 microM). Sustained MDMA exposure augmented MDMA-induced serotonin release in a concentration-dependent manner, indicating serotonergic sensitization. Similar serotonergic sensitization was observed for METH. The development of MDMA-induced serotonergic sensitization was attenuated by the NMDA receptor antagonist, MK-801 (10 microM). These results suggest that in mesencephalic slice cultures sustained MDMA or METH exposure induces serotonergic sensitization through activation of NMDA receptors without serotonergic neurotoxicity. The in vitro model system could help to elucidate the mechanisms underlying drug addiction.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 3
- Psychedelic Therapy: A Primer for Primary Care Clinicians-3,4-Methylenedioxy-methamphetamine (MDMA). American Journal of Therapeutics
- Sustained exposure to 3,4-methylenedioxymethamphetamine induces the augmentation of exocytotic serotonin release in rat organotypic raphe slice cultures. Journal of Pharmacological Sciences May 19, 2010
- MDMA ("ecstasy") impairs learning in the Morris Water Maze and reduces hippocampal LTP in young rats. Neuroscience Letters January 29, 2010
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