Activation of glycogen phosphorylase by serotonin and 3,4-methylenedioxymethamphetamine in astroglial-rich primary cultures: involvement of the 5-HT2A receptor
Jose C Poblete, Efrain C. Azmitia
Brain Research May 1, 1995 DOI: 10.1016/0006-8993(95)00201-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat brain astroglial-rich primary cell culture |
| Interventions | MDMA(+) Serotonin (5-HT) DOB Mianserin |
| Dose | 5-HT: 100 nM–100 μM; MDMA(+): 500 nM–50 μM; DOB: 100 nM; mianserin: 200 nM |
| Topics | MDMA Serotonin |
| Citations | 52 |
| Key findings | Serotonin, MDMA, and the 5-HT2 agonist DOB each increased active glycogen phosphorylase in astroglial cultures, and these increases were attenuated by the 5-HT2 antagonist mianserin. The authors propose that MDMA elevates synaptic serotonin, driving glycogenolysis through 5-HT2 receptor activation, and that prolonged GPase activity may deplete synaptic energy stores and contribute to terminal degeneration caused by substituted amphetamines. |
Abstract
Neurotransmitters, neuropeptides, and ions regulate glycogen levels in the brain by modulating the activity of glycogen synthase (GSase) and glycogen phosphorylase (GPase). GPase is co-localized with glial fibrillary acidic protein (GFAP), an astroglia-specific marker, suggesting that glycogen is localized in astroglial cells. Additionally, functional serotonin (5-HT) receptors are found in both neurons and glia, and 5-HT is known to stimulate glycogenolysis. It is reported that 3,4-methylenedioxymethamphetamine (MDMA), a drug of abuse, stimulates the release and inhibits the reuptake of 5-HT, and selectively inhibits the activity of MAO-A. These biochemical consequences of MDMA lead to increased extra-cellular 5-HT levels. This study investigates the effects of MDMA(+) and serotonin (5-HT) on glycogen metabolism in the rat brain. A histochemical method was designed to visualize active glycogen phosphorylase (GPase) in an astroglial-rich primary culture. Serotonin activated GPase in a concentration-dependent manner (100 nM−100 μM). Maximal activation by 5-HT was achieved by 50 μM and resulted in a 167% increase in the number of reactive sites (P < 0.001). MDMA(+) (500 nM−50 μM) directly stimulated GPase activity with maximal activation induced by 5 μM, which caused a 70% increase in the number of reactive sites (P < 0.001). The 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB), also displayed a concentration-dependent increase in the number of GPase reactive sites. Maximal stimulation by DOB occurred at 100 nM which increased the number of reactive sites by 166% (P < 0.001). These effects of 5-HT and MDMA(+) were significantly attenuated by mianserin (200 nM), a 5-HT2 receptor antagonist. An astrocyte-neuron metabolic link may be vital for synaptic homeostasis. By increasing 5-HT levels in the synapse, MDMA(+) may increase GPase activity and promote glycogenolysis via activation of the 5-HT2 receptor. Prolonged GPase activity may lead to depletion of synaptic energy stores, thereby compromising the energy state of the synapse. The resulting deficiency in synaptic energy may contribute to terminal degeneration induced by substituted amphetamines.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 11
- Cerebral1H MRS alterations in recreational 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) users Journal of Magnetic Resonance Imaging October 1, 1999
- α-Lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity Neuroreport November 1, 1999
- Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: Temporal, spatial, and cellular patterns The Journal of Comparative Neurology 2006
- Cerebral 1H MRS alterations in recreational 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) users Journal of Magnetic Resonance Imaging October 1, 1999
- Psychedelics in the Treatment of Neurologic and Psychiatric Disorders: Coincidence or a New Point of View. Molecular Neurobiology June 4, 2025
and 6 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
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Journal of Medicinal Chemistry May 1, 1982
- MDMA (ecstasy) effects on cultured serotonergic neurons: evidence for Ca2+-dependent toxicity linked to release Brain Research February 1, 1990
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