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Acute effects of 4-EA-NBOMe, 3, 4-DCMP, LY-2183240 and AB-CHFUPYCA on the excitability of rat cortical primary cultured neurons

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Abstract

Background

Various methods to evaluate the effect of new psychoactive substances (NPSs) on the central nervous system (CNS) are available, but they are not sufficient. There is an urgent need for a method to measure and analyze the effect of NPS on the CNS for scientific research.

Objectives

We investigated whether seven psychoactive substances (PSs) affect the excitability of rat cortical culture neurons by counting the number of action potentials (APs) in current clamp modes.

Results

Incubation with Meth, THC, LY2183240 and AB-CHFUPYCA for 2 min increased the number of APs; in contrast, incubation with 4-EA-NBOMe and CMP reduced the number of APs. Cocaine did not show any effects on the number of APs.

Conclusion

Acute treatment with PSs changed neural excitability as evidenced by the number of APs. Our data provide scientific evidence that acute PS exposure can affect the CNS.

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Abbreviations

Meth (Methamphetamine):

(RS)-N-methyl-1-phenylpropan-2-amine

4-EA-NBOMe (N-(ortho-methoxybenzyl)-4-ethylamphetamine):

1-(4-Ethylphenyl)-N-[(2-methoxyphenyl)methyl]propan-2-amine

3, 4-DCMP (3, 4-dichloromethylphenidate):

Methyl (2R)-2-(3,4-dichlorophenyl)-2-[(2R)-piperidin-2-yl]acetate

THC (Δ1-tetrahydrocannabinol):

(6AR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol

LY-2183240 (5-(4-biphenylylmethyl)-N,N-dimethyl-1H-tetrazole-1-carboxamide):

N,N-Dimethyl-5-[(4-biphenyl)methyl]tetrazole-1-carboxamide

AB-CHFUPYCA:

N-(1-Amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide

Cocaine:

Methyl (1R,2R,3S,5S)-3-(benzoyloxy)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

References

  • Avchalumov Y, Trenet W, Pina-Crespo J, Mandyam C (2020) SCH23390 reduces methamphetamine self-administration and prevents methamphetamine-induced striatal LTD. Int J Mol Sci 21:6491

    Article  CAS  Google Scholar 

  • Elliott SP, Holdbrook T, Brandt SD (2020) Prodrugs of new psychoactive substances (NPS): a new challenge. J Forensic Sci 65:913–920

    Article  Google Scholar 

  • Evans-Brown M, Sedefov R (2017) New psychoactive substances: driving greater complexity into the drug problem. Addiction 112:36–38

    Article  Google Scholar 

  • Feng LY, Li JH (2020) New psychoactive substances in Taiwan: challenges and strategies. Curr Opin Psychiatry 33:306–311

    Article  Google Scholar 

  • Franz F, Angerer V, Brandt SD, McLaughlin G, Kavanagh PV, Moosmann B, Auwarter V (2017) In vitro metabolism of the synthetic cannabinoid 3,5-AB-CHMFUPPYCA and its 5,3-regioisomer and investigation of their thermal stability. Drug Test Anal 9:311–316

    Article  CAS  Google Scholar 

  • Friend L, Weed J, Sandoval P, Nufer T, Ostlund I, Edwards JG (2017) CB1-dependent long-term depression in ventral tegmental area GABA neurons: a novel target for Marijuana. J Neurosci 37:10943–10954

    Article  CAS  Google Scholar 

  • Guirguis A (2017) New psychoactive substances: a public health issue. Int J Pharm Pract 25:323–325

    Article  Google Scholar 

  • Jo S, Yarishkin O, Hwang YJ, Chun YE, Park M, Woo DH, Bae JY, Kim T, Lee J, Chun H, Park HJ, Lee DY, Hong J, Kim HY, Oh SJ, Park SJ, Lee H, Yoon BE, Kim Y, Jeong Y, Shim I, Bae YC, Cho J, Kowall NW, Ryu H, Hwang E, Kim D, Lee CJ (2014) GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease. Nat Med 20:886–896

    Article  CAS  Google Scholar 

  • Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D (2014) Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 82:1556–1563

    Article  Google Scholar 

  • Lee CJ, Mannaioni G, Yuan H, Woo DH, Gingrich MB, Traynelis SF (2007) Astrocytic control of synaptic NMDA receptors. J Physiol 581:1057–1081

    Article  CAS  Google Scholar 

  • Luethi D, Kaeser PJ, Brandt SD, Krahenbuhl S, Hoener MC, Liechti ME (2018) Pharmacological profile of methylphenidate-based designer drugs. Neuropharmacology 134:133–140

    Article  CAS  Google Scholar 

  • Nedergaard M, Takano T, Hansen AJ (2002) Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3:748–755

    Article  CAS  Google Scholar 

  • Peacock A, Bruno R, Gisev N, Degenhardt L, Hall W, Sedefov R, White J, Thomas KV, Farrell M, Griffiths P (2019) New psychoactive substances: challenges for drug surveillance, control, and public health responses. Lancet 394:1668–1684

    Article  Google Scholar 

  • Pena-Bravo JI, Penrod R, Reichel CM, Lavin A (2019) Methamphetamine self-administration elicits sex-related changes in postsynaptic glutamate transmission in the prefrontal cortex. eNeuro 6(1):1–11

    Article  Google Scholar 

  • Report, W. D. United Nations Office on Drugs and Crime

  • Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41

    Article  CAS  Google Scholar 

  • Rubenstein JL, Merzenich MM (2003) Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2:255–267

    Article  CAS  Google Scholar 

  • Schifano F, Napoletano F, Chiappini S, Guirguis A, Corkery JM, Bonaccorso S, Ricciardi A, Scherbaum N, Vento A (2021) New/emerging psychoactive substances and associated psychopathological consequences—corrigendum. Psychol Med 51:43

    Article  CAS  Google Scholar 

  • Siemsen BM, Reichel CM, Leong KC, Garcia-Keller C, Gipson CD, Spencer S, McFaddin JA, Hooker KN, Kalivas PW, Scofield MD (2019) Effects of methamphetamine self-administration and extinction on astrocyte structure and function in the nucleus accumbens core. Neuroscience 406:528–541

    Article  CAS  Google Scholar 

  • Tutka P, Wlaz A, Florek-Luszczki M, Kolodziejczyk P, Bartusik-Aebisher D, Luszczki JJ (2018) Arvanil, olvanil, AM 1172 and LY 2183240 (various cannabinoid CB1 receptor agonists) increase the threshold for maximal electroshock-induced seizures in mice. Pharmacol Rep 70:106–109

    Article  CAS  Google Scholar 

  • Westphal F, Girreser U, Waldmuller D (2016) Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs. Drug Test Anal 8:910–919

    Article  CAS  Google Scholar 

  • Woo DH, Han KS, Shim JW, Yoon BE, Kim E, Bae JY, Oh SJ, Hwang EM, Marmorstein AD, Bae YC, Park JY, Lee CJ (2012) TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell 151:25–40

    Article  CAS  Google Scholar 

  • Zhang S, Jin Y, Liu X, Yang L, Ge Z, Wang H, Li J, Zheng J (2014) Methamphetamine modulates glutamatergic synaptic transmission in rat primary cultured hippocampal neurons. Brain Res 1582:1–11

    Article  CAS  Google Scholar 

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Acknowledgements

Mr. Choi, Chang-Hoon supported the production of primary cultured rat cortical neurons.

Funding

This work was supported by Grant 20182MFDS423 from the Ministry of Food and Drug Safety in 2021, by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1F1A1060137), by R&D Convergence Program of the National Research Council of Science and Technology (NST) Grant (CAP-18-02-KRIBB) of Republic of Korea and by Korea Institute of Toxicology (KIT) Research Program (KK-2212).

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Authors

Contributions

OHA: electrophysiology experiments, draft writing. LJH: data discussion, manuscript review. WDH: manuscript writing, data investigation and project supervision.

Corresponding author

Correspondence to Dong Ho Woo.

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Author Hyun-A Oh declares that he has no conflict of interest. Author Jong-Hwa Lee declares that he has no conflict of interest. Author Dong Ho Woo declares that he has no conflict of interest.

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This article does not contain any experiments with human participants or animals performed by any of the authors.

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Oh, HA., Lee, JH. & Woo, D.H. Acute effects of 4-EA-NBOMe, 3, 4-DCMP, LY-2183240 and AB-CHFUPYCA on the excitability of rat cortical primary cultured neurons. Mol. Cell. Toxicol. 18, 531–538 (2022). https://doi.org/10.1007/s13273-022-00224-2

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