Masaki Domoto1, Hitoki Sasase1, Shintaro Wada1, Shiho Ito1, Satoshi Deyama1, Eiichi Hinoi1, Shuji Kaneko2, Katsuyuki Kaneda3. 1. Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. 2. Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan. 3. Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan. k-kaneda@p.kanazawa-u.ac.jp.
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.
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.
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