Chronic 3,4-methylenedioxymethamphetamine administration decreases glucocorticoid and mineralocorticoid receptor, but increases 5-hydroxytryptamine1C receptor gene expression in the rat hippocampus.
J L Yau, P A Kelly, J Sharkey, J R Seckl
Neuroscience July 1994 DOI: 10.1016/0306-4522(94)90057-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | 3 |
| Dose | 20 mg/kg twice daily for four days, subcutaneous |
| Duration | Four-day dosing regimen; measurements two weeks after |
| Measures | in situ hybridization histochemistry for glucocorticoid receptor, mineralocorticoid receptor, 5-HT1A, 5-HT1C, and 5-HT2 receptor messenger RNA; corticosterone levels; thymic and adrenal weights; corticosterone-binding globulin levels |
| Topics | MDMA |
| Key findings | Repeated MDMA (20 mg/kg twice daily for four days) in rats reduced hippocampal glucocorticoid and mineralocorticoid receptor messenger RNA by 30-47% two weeks later and increased 5-HT1C receptor messenger RNA by 133% in CA3, with no changes in 5-HT1A or 5-HT2 receptor messenger RNA. The authors suggest serotonergic innervation maintains hippocampal corticosteroid receptor gene expression, possibly through 5-HT1C receptors. |
Abstract
Both glucocorticoids and serotonin have been implicated in the regulation of mood and neuroendocrine control. In this study we have examined the effects of the psychomotor stimulant, 3,4-methylenedioxymethamphetamine on corticosteroid and 5-hydroxytryptamine receptor subtype gene expression within the hippocampal formation using in situ hybridization histochemistry. Animals were injected subcutaneously with 3,4-methylenedioxymethamphetamine (20 mg/kg) twice daily for four days. Two weeks following this dosage regimen, shown to markedly reduce 5-hydroxytryptamine terminals, both glucocorticoid receptor and mineralocorticoid receptor messenger RNA expression were significantly decreased (30-47% fall) in the granule cells of the dentate gyrus and pyramidal cells of CA1-CA4 fields of Ammon's horn, but not in parietal cortex neurons. In the same rats, 5-hydroxytryptamine1C receptor messenger RNA expression was significantly increased in CA3 pyramidal neurons (133% rise), but neither 5-hydroxytryptamine1A or 5-hydroxytryptamine2 receptor messenger RNA levels were altered in any dorsal hippocampal subfield. 3,4-Methylenedioxymethamphetamine treatment was associated with modest hypersecretion of coricosterone during the diurnal nadir, without other peripheral evidence of chronic glucocorticoid excess (unchanged thymic and adrenal weights and corticosterone-binding globulin levels). These results emphasize the importance of the serotonergic innervation in maintaining hippocampal corticosteroid receptor gene expression. It is suggested that 5-hydroxytryptamine1C receptors may be involved in mediating the effects of serotonin on hippocampal glucocorticoid receptor and mineralocorticoid receptor expression and perhaps mood.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 6
- Differential long-term effects of MDMA on the serotoninergic system and hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice The International Journal of Neuropsychopharmacology July 9, 2008
- Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications Pharmaceuticals June 17, 2011
- Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers. Neurotoxicology July 2015
- Multiple molecular and neuropharmacological effects of MDMA (Ecstasy). Life Sciences January 2, 2004
- Activation of protein kinase C (PKC) by 3,4-methylenedioxymethamphetamine (MDMA) occurs through the stimulation of serotonin receptors and transporter. Neuropsychopharmacology September 1997
and 1 more in the library
Cites 8
- Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Journal of Neuroscience August 1, 1988
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- Neuroanatomic specificity and time course of alterations in rat brain serotonergic pathways induced by MDMA (3,4‐methylenedioxymethamphetamine): Assessment using quantitative autoradiography Synapse August 1, 1991
- Neuroendocrine and Mood Responses to Intravenous L-Tryptophan in 3,4-Methylenedioxymethamphetamine (MDMA) Users Archives of General Psychiatry 1989
- Repeated administration of MDMA causes transient down-regulation of serotonin 5-HT2 receptors. Neuropharmacology September 1992
and 3 more in the library