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Psychopharmacology

, Volume 235, Issue 8, pp 2367–2376 | Cite as

The synthetic cannabinoid 5F-AMB changes the balance between excitation and inhibition of layer V pyramidal neurons in the mouse medial prefrontal cortex

  • Masaki Domoto
  • Hitoki Sasase
  • Shintaro Wada
  • Shiho Ito
  • Satoshi Deyama
  • Eiichi Hinoi
  • Shuji Kaneko
  • Katsuyuki Kaneda
Original Investigation
  • 101 Downloads

Abstract

Rationale

5F-AMB is one of the synthetic cannabinoids (SCs) designed to potentiate the ability to activate cannabinoid 1 (CB1) receptors and is abused worldwide. Although inhalation of 5F-AMB elicits serious adverse effects including impaired memory and consciousness, it is not known whether and how 5F-AMB affects the activity of pyramidal neurons in the medial prefrontal cortex (mPFC), a brain region associated with higher functions such as memory and cognition.

Objectives

In the present study, we examined the effects of 5F-AMB on mPFC layer V (L5) pyramidal neurons using in vitro whole-cell patch-clamp recordings.

Results

Bath application of 5F-AMB attenuated the frequency but not the amplitude of spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs). The attenuating effects of 5F-AMB were abolished by the CB1 receptor antagonist AM251. 5F-AMB also attenuated the frequency of miniature EPSCs and IPSCs recorded in the presence of tetrodotoxin. Moreover, the extent of attenuating effects of 5F-AMB on stimulus-evoked EPSCs was significantly larger than that on evoked IPSCs.

Conclusions

These findings suggest that 5F-AMB attenuates both excitatory and inhibitory transmission in mPFC L5 pyramidal neurons via the activation of CB1 receptors located in presynaptic terminals. Further, the net impact of 5F-AMB on L5 pyramidal neurons is inhibition due to the change in balance between excitation and inhibition. This inhibitory effect might at least partly contribute to the expression of the adverse effects induced by 5F-AMB inhalation.

Keywords

5F-AMB Synthetic cannabinoids Designer drug Medial prefrontal cortex CB1 receptor Layer V pyramidal neurons 

Notes

Acknowledgements

This study was supported by Grant-in-Aid for Scientific Research (C) (K.K., 15K06765) from the Japan Society for the Promotion of Science (JSPS), Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sport, Science and Technology of Japan (S.K., 15K15182), grant from Suzuken Memorial Foundation (K.K.), and the Kurata Grant awarded by the Hitachi Global Foundation (K.K.).

Compliance with Ethical Standards

All experiments were conducted in accordance with the National Institutes of Health guidelines and performed with the approval of the Institutional Animal Care and Use Committee at Kanazawa University.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

References

  1. Andersson M, Diao X, Wohlfarth A, Scheidweiler KB, Huestis MA (2016) Metabolic profiling of new synthetic cannabinoids AMB and 5F-AMB by human hepatocyte and liver microsome incubations and high-resolution mass spectrometry. Rapid Commun Mass Spectrom 30:1067–1078CrossRefPubMedGoogle Scholar
  2. Araque A, Castillo PE, Manzoni OJ, Tonini R (2017) Synaptic functions of endocannabinoid signaling in health and disease. Neuropharmacology 124:13–24CrossRefPubMedGoogle Scholar
  3. Asaoka N, Kawai H, Nishitani N, Kinoshita H, Shibui N, Nagayasu K, Shirakawa H, Kaneko S (2016) A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons. J Toxicol Sci 41:813–816CrossRefPubMedGoogle Scholar
  4. Auclair N, Otani S, Soubrie P, Crepel F (2000) Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons. J Neurophysiol 83:3287–3293CrossRefPubMedGoogle Scholar
  5. Banister SD, Longworth M, Kevin R, Sachdev S, Santiago M, Stuart J, Mack JB, Glass M, McGregor IS, Connor M, Kassiou M (2016) Pharmacology of valinate and tert-leucinate synthetic cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and their analogues. ACS Chem Neurosci 7:1241–1254CrossRefPubMedGoogle Scholar
  6. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA (2014) Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 144:12–41CrossRefPubMedGoogle Scholar
  7. Chiu CQ, Puente N, Grandes P, Castillo PE (2010) Dopaminergic modulation of endocannabinoid-mediated plasticity at GABAergic synapses in the prefrontal cortex. J Neurosci 30:7236–7248CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chocyk A, Majcher-Maślanka I, Dudys D, Przyborowska A, Wędzony K (2013) Impact of early-life stress on the medial prefrontal cortex functions - a search for the pathomechanisms of anxiety and mood disorders. Pharmacol Rep 65:1462–1470CrossRefPubMedGoogle Scholar
  9. Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784CrossRefPubMedGoogle Scholar
  10. Debruyne D, Le Boisselier R (2015) Emerging drugs of abuse: current perspectives on synthetic cannabinoids. Subst Abuse Rehabil 6:113–129CrossRefPubMedPubMedCentralGoogle Scholar
  11. Egerton A, Allison C, Brett RR, Pratt JA (2006) Cannabinoids and prefrontal cortical function: insights from preclinical studies. Neurosci Biobehav Rev 30:680–695CrossRefPubMedGoogle Scholar
  12. Euston DR, Gruber AJ, McNaughton BL (2012) The role of medial prefrontal cortex in memory and decision making. Neuron 76:1057–1070CrossRefPubMedPubMedCentralGoogle Scholar
  13. Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066CrossRefPubMedGoogle Scholar
  14. Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492:145–177CrossRefPubMedGoogle Scholar
  15. Guo J, Ikeda SR (2004) Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB1 cannabinoid receptors heterologously expressed in mammalian neurons. Mol Pharmacol 65:665–674CrossRefPubMedGoogle Scholar
  16. Haider B, Duque A, Hasenstaub AR, McCormick DA (2006) Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. J Neurosci 26:4535–4545CrossRefPubMedGoogle Scholar
  17. Kaneko S (2017) Motor vehicle collisions caused by the 'super-strength' synthetic cannabinoids, MAM-2201, 5F-PB-22, 5F-AB-PINACA, 5F-AMB and 5F-ADB in Japan experienced from 2012 to 2014. Forensic Toxicol 35:244–251CrossRefPubMedPubMedCentralGoogle Scholar
  18. Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M (2009) Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 89:309–380CrossRefPubMedGoogle Scholar
  19. Kouneiher F, Charron S, Koechlin E (2009) Motivation and cognitive control in the human prefrontal cortex. Nat Neurosci 12:939–945CrossRefPubMedGoogle Scholar
  20. Kucewicz MT, Tricklebank MD, Bogacz R, Jones MW (2011) Dysfunctional prefrontal cortical network activity and interactions following cannabinoid receptor activation. J Neurosci 31:15560–15568CrossRefPubMedGoogle Scholar
  21. Lafourcade M, Elezgarai I, Mato S, Bakiri Y, Grandes P, Manzoni OJ (2007) Molecular components and functions of the endocannabinoid system in mouse prefrontal cortex. PLoS One 2:e709.  https://doi.org/10.1371/journal.pone.0000709 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Lutz B, Marsicano G, Maldonado R, Hillard CJ (2015) The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci 16:705–718CrossRefPubMedPubMedCentralGoogle Scholar
  23. Morena M, Campolongo P (2014) The endocannabinoid system: an emotional buffer in the modulation of memory function. Neurobiol Learn Mem 112:30–43CrossRefPubMedGoogle Scholar
  24. Morici JF, Bekinschtein P, Weisstaub NV (2015) Medial prefrontal cortex role in recognition memory in rodents. Behav Brain Res 292:241–251CrossRefPubMedGoogle Scholar
  25. den Boon FS, Werkman TR, Schaafsma-Zhao Q, Houthuijs K, Vitalis T, Kruse CG, Wadman WJ, Chameau P (2015) Activation of type-1 cannabinoid receptor shifts the balance between excitation and inhibition towards excitation in layer II/III pyramidal neurons of the rat prelimbic cortex. Pflugers Arch 467:1551–1564CrossRefGoogle Scholar
  26. Otis JM, Dashew KB, Mueller D (2013) Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory. J Neurosci 33:1271–1281CrossRefPubMedPubMedCentralGoogle Scholar
  27. Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147:S163–S171CrossRefPubMedPubMedCentralGoogle Scholar
  28. Seely KA, Lapoint J, Moran JH, Fattore L (2012) Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 39:234–243CrossRefPubMedPubMedCentralGoogle Scholar
  29. Steindel F, Lerner R, Häring M, Ruehle S, Marsicano G, Lutz B, Monory K (2013) Neuron-type specific cannabinoid-mediated G protein signalling in mouse hippocampus. J Neurochem 124:795–807CrossRefPubMedGoogle Scholar
  30. Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran(2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar
  31. Wegener N, Kuhnert S, Thüns A, Roese R, Koch M (2008) Effects of acute systemic and intra-cerebral stimulation of cannabinoid receptors on sensorimotor gating, locomotion and spatial memory in rats. Psychopharmacology (Berl) 198:375–385CrossRefGoogle Scholar
  32. Xu C, Hermes DJ, Mackie K, Lichtman AH, Ignatowska-Jankowska BM, Fitting S (2016) Cannabinoids occlude the HIV-1 Tat-induced decrease in GABAergic neurotransmission in prefrontal cortex slices. J Neuroimmune Pharmacol 11:316–331CrossRefPubMedPubMedCentralGoogle Scholar
  33. Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, Sohal VS, Goshen I, Finkelstein J, Paz JT, Stehfest K, Fudim R, Ramakrishnan C, Huguenard JR, Hegemann P, Deisseroth K (2011) Neocortical excitation/inhibition balance in information processing and social dysfunction. Nature 477:171–178CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health SciencesKanazawa UniversityKanazawaJapan
  2. 2.Department of Molecular Pharmacology, Graduate School of Pharmaceutical SciencesKyoto UniversityKyotoJapan

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