Changes in neuronal activity in rat primary cortical cultures induced by illicit drugs and new psychoactive substances (NPS) following prolonged exposure and washout to mimic human exposure scenarios

Zwartsen, Anne; Hondebrink, Laura; Westerink, Remco H.S.

doi:10.1016/j.neuro.2019.05.004

Cited by 22 publications

(58 citation statements)

References 22 publications

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“…propan-1-one), methylone (1-(1,3-benzodioxol-5-yl)-2-(methy lamino)propan-1-one), pentedrone (2-(methylamino)-1-phenyl pentan-1-one), and MDPV (1-(1,3-benzodioxol-5-yl)-2-pyrro lidin-1-ylpentan-1-one) hydrochloride salts (purity > 98.5%) were obtained from Lipomed (Weil am Rhein, Germany). Data on α-PVP were published previously (Zwartsen et al, 2017(Zwartsen et al, , 2019. 3-MMC and 4-MEC were also purchased from a commercial website for "research chemicals" and are described in this article as 3-MMC internet and 4-MEC internet .…”

Section: Chemicalsmentioning

confidence: 99%

“…Cell viability was determined as described in Zwartsen et al (2019). In short, medium and lysis buffer were removed from all wells after which 100 µL NR solution (Invitrogen, Breda, Netherlands; 12 µM in phenol-red free NB-A medium w/o supplements) was added to the cells.…”

Section: Cell Viability Of Hek 293 Cellsmentioning

confidence: 99%

“…In previous research, the applicability of neuronal cultures grown on microelectrode arrays (MEAs) as an efficient screening tool to determine the neurotoxicity of pharmaceuticals, toxins, illicit drugs, and NPS was shown (Dingemans et al, 2016;Vassallo et al, 2017;Strickland et al, 2018;Zwartsen et al, 2018Zwartsen et al, , 2019. MEA measurements allow for determining effects of synthetic cathinones on spontaneous neuronal network activity, thereby including a range of neuronal targets in a single assay.…”

Section: Introductionmentioning

confidence: 99%

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Hazard Characterization of Synthetic Cathinones Using Viability, Monoamine Reuptake, and Neuronal Activity Assays

et al. 2020

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Section: Chemicalsmentioning

confidence: 99%

Section: Cell Viability Of Hek 293 Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hazard Characterization of Synthetic Cathinones Using Viability, Monoamine Reuptake, and Neuronal Activity Assays

et al. 2020

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“…The compound was 10-fold more potent than its precursor, 2C-B. Importantly, neuronal activity did not recover after 19 h of washout following prolonged exposure to 10 and 30 µM of 25B-NBOMe (Zwartsen et al, 2019).…”

Section: Toxicity In Vitromentioning

confidence: 89%

“…The neurotoxic action of 25C-NBOMe involves activation of the MAP/ERK cascade and inhibition of the Akt pathway (Xu et al, 2019). Acute (30 min) and prolonged (5 h) exposure of primary rat cortical cultures to 25B-NBOMe decreased spontaneous neuronal activity, measured as firing rate and burst rate (Zwartsen et al, 2018(Zwartsen et al, , 2019. The compound was 10-fold more potent than its precursor, 2C-B.…”

Section: Toxicity In Vitromentioning

confidence: 99%

NBOMes–Highly Potent and Toxic Alternatives of LSD

2020

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Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT 2A and 5-HT 2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT 2A compared with 5-HT 1A. They display higher affinity for 5-HT 2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT 2B receptor compared to 5-HT 2A or 5-HT 2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of nonfatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.

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Culture of Rat Primary Cortical Cells for Microelectrode Array (MEA) Recordings to Screen for Acute and Developmental Neurotoxicity

et al. 2021

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Neurotoxicity testing of chemicals, drug candidates, and environmental pollutants still relies on extensive in vivo studies that are very costly, time‐consuming, and ethically debated due to the large number of animals typically used. Currently, rat primary cortical cultures are widely used for in vitro neurotoxicity studies, as they closely resemble the in vitro brain with respect to the diversity of cell types, their physiological functions, and the pathological processes that they undergo. Common in vitro assays for neurotoxicity screening often focus on very target‐specific endpoints such as morphological, biochemical, or electrophysiological changes, and such narrow focus can hamper translation and interpretation. Microelectrode array (MEA) recordings provide a non‐invasive platform for extracellular recording of electrical activity of cultured neuronal cells, thereby enabling the evaluation of changes in neuronal (network) function as a sensitive and integrated endpoint for neurotoxicity screening. Here, we describe an in vitro approach for assessing changes in neuronal network function as a measure for neurotoxicity, using rat primary cortical cultures grown on MEAs. We provide a detailed protocol for the culture of rat primary cortical cells, and describe several experimental procedures to address acute, subchronic, and chronic exposure scenarios. We additionally describe the steps for processing and analyzing MEA and cell viability data. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Isolation and culture of rat primary cortical cells on 48‐well MEA plates Support Protocol 1: Pretreatment and washing of 48‐well MEA plates before first use or for re‐use Support Protocol 2: Coating of 48‐well MEA plates with 0.1% PEI solution Basic Protocol 2: MEA measurements during acute exposure Alternate Protocol 1: MEA measurements during subchronic exposure Alternate Protocol 2: MEA measurements during chronic exposure Support Protocol 3: Determination of cell viability after MEA experiments Basic Protocol 3: MEA data processing Basic Protocol 4: Analyzing MEA experiments after acute and subchronic exposure Alternate Protocol 3: Analyzing MEA experiments after chronic exposure

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Changes in neuronal activity in rat primary cortical cultures induced by illicit drugs and new psychoactive substances (NPS) following prolonged exposure and washout to mimic human exposure scenarios

Cited by 22 publications

References 22 publications

Hazard Characterization of Synthetic Cathinones Using Viability, Monoamine Reuptake, and Neuronal Activity Assays

Hazard Characterization of Synthetic Cathinones Using Viability, Monoamine Reuptake, and Neuronal Activity Assays

NBOMes–Highly Potent and Toxic Alternatives of LSD

Culture of Rat Primary Cortical Cells for Microelectrode Array (MEA) Recordings to Screen for Acute and Developmental Neurotoxicity

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