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The synthetic cannabinoid 5F-AMB changes the balance between excitation and inhibition of layer V pyramidal neurons in the mouse medial prefrontal cortex
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The synthetic cannabinoid 5F-AMB changes the balance between excitation and inhibition of layer V pyramidal neurons in the mouse medial prefrontal cortex
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Journal Article
The synthetic cannabinoid 5F-AMB changes the balance between excitation and inhibition of layer V pyramidal neurons in the mouse medial prefrontal cortex
2018
Overview
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.
Publisher
Springer Berlin Heidelberg,Springer,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Brain
/ Excitatory postsynaptic potentials
/ Excitatory Postsynaptic Potentials - drug effects
/ Excitatory Postsynaptic Potentials - physiology
/ Female
/ Inhibitory postsynaptic potentials
/ Inhibitory Postsynaptic Potentials - drug effects
/ Inhibitory Postsynaptic Potentials - physiology
/ Male
/ Memory
/ Mice
/ Patch-Clamp Techniques - methods
/ Prefrontal Cortex - cytology
/ Prefrontal Cortex - drug effects
/ Prefrontal Cortex - physiology
/ Presynaptic Terminals - drug effects
/ Presynaptic Terminals - physiology
/ Pyramidal Cells - drug effects
