Methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) induce differential cytotoxic effects in bovine brain microvessel endothelial cells
H. Rosas-Hernández, Elvis Cuevas, Susan M. Lantz, K. Rice, Brenda M. Gannon, William E Fantegrossi, C. Gonzalez, Merle G. Paule, Syed F. Ali
Neuroscience Letters June 16, 2016 DOI: 10.1016/j.neulet.2016.06.029 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Bovine brain microvessel endothelial cells (bBMVECs), an in vitro model of the blood-brain barrier |
| Interventions | Methamphetamine (METH) MDMA MDPV |
| Dose | 0.5 mM - 2.5 mM |
| Duration | 24 hours |
| Measures | lactate dehydrogenase release, cellular proliferation, reactive oxygen species production, nitric oxide production, morphological analysis |
| Topics | MDMA |
| Key points | METH, MDMA, and MDPV each damaged blood-brain barrier endothelial cells in vitro, but by different mechanisms and with different potency. MDPV was the most toxic, inducing cytotoxicity and reactive oxygen species at all tested concentrations (0.5-2.5 mM) and monolayer disruption from 0.5 mM, whereas METH and MDMA showed cytotoxicity and reduced proliferation only at 2.5 mM. All three increased nitric oxide production. |
Abstract
Designer drugs such as synthetic psychostimulants are indicative of a worldwide problem of drug abuse and addiction. In addition to methamphetamine (METH), these drugs include 3,4- methylenedioxy-methamphetamine (MDMA) and commercial preparations of synthetic cathinones including 3,4-methylenedioxypyrovalerone (MDPV), typically referred to as “bath salts.” These psychostimulants exert neurotoxic effects by altering monoamine systems in the brain. Additionally, METH and MDMA adversely affect the integrity of the blood-brain barrier (BBB): there are no current reports on the effects of MDPV on the BBB. The aim of this study was to compare the effects of METH, MDMA and MDPV on bovine brain microvessel endothelial cells (bBMVECs), an accepted in vitro model of the BBB. Confluent bBMVEC monolayers were treated with METH, MDMA and MDPV (0.5 mM - 2.5 mM) for 24 hours. METH and MDMA increased lactate dehydrogenase release only at the highest concentration (2.5 mM), whereas MDPV induced cytotoxicity at all concentrations. MDMA and METH decreased cellular proliferation only at 2.5 mM, with similar effects observed after MDPV exposures starting at 1 mM. Only MDPV increased reactive oxygen species production at all concentrations tested whereas all 3 drugs increased nitric oxide production. Morphological analysis revealed different patterns of compound-induced cell damage. METH induced vacuole formation at 1 mM and disruption of the monolayer at 2.5 mM. MDMA induced disruption of the endothelial monolayer from 1 mM without vacuolization. On the other hand, MDPV induced monolayer disruption at doses ≥ 0.5 mM without vacuole formation; at 2.5 mM, the few remaining cells lacked endothelial morphology. These data suggest that even though these synthetic psychostimulants alter monoaminergic systems, they each induce BBB toxicity by different mechanisms with MDPV being the most toxic.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 2
- Effects of ambient temperature on locomotor activity and place conditioning elicited by abused psychostimulants in mice: Role of 3,4-methylenedioxy moiety. Drug and Alcohol Dependence September 1, 2023
- DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants. ACS Chemical Neuroscience May 11, 2018
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