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
Psychopharmacology August 1, 2018 DOI: 10.1007/s00213-018-4933-5 via PubMed
Summary
AI-generated from the abstract5F-AMB, a synthetic cannabinoid abused worldwide, reduces both excitatory and inhibitory signaling in layer V pyramidal neurons of the medial prefrontal cortex by activating CB1 receptors on presynaptic terminals. Bath application of 5F-AMB decreased the frequency of spontaneous and miniature excitatory and inhibitory postsynaptic currents, an effect blocked by the CB1 antagonist AM251. The suppression of excitatory transmission was greater than that of inhibitory transmission, shifting the balance toward net inhibition of these neurons. This inhibitory effect may contribute to the memory and consciousness impairments observed after inhalation of 5F-AMB.
Study at a glance
| Characteristics | In vitro electrophysiological study Peer reviewed |
|---|---|
| Population | Layer V pyramidal neurons from the medial prefrontal cortex of rats (implied by typical slice preparation, but not explicitly stated in abstract) |
| Intervention | 5F-AMB |
| Keywords | 5f-amb Cb1 receptor Designer drug Medial prefrontal cortex Synthetic cannabinoids |
| Key finding | 5F-AMB attenuates both excitatory and inhibitory synaptic transmission in mPFC layer V pyramidal neurons via presynaptic CB1 receptor activation, with a net inhibitory effect due to greater suppression of excitation. |
Abstract
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. 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. 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. 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.