Bi LL,Â Chen M,Â Pei L,Â Shu S,Â Jin HJ,Â Yan HL,Â Wei N,Â Wang S,Â Yang X,Â Yan HH,Â Xu MM,Â Yao CY,Â Li N,Â Tang N,Â Wu JH,Â Zhu HZ,Â Li H,Â Cai Y,Â Guo Y,Â Shi Y,Â Tian Q, Zhu LQ,Â Lu YM, Mol Neurobiol.Â 2015 Apr 22. [Epub ahead of print]
Endothelin1 (ET1) is a potent vasoconstrictor that is also known to be aÂ neuropeptideÂ that is involved in neural circuits. We examined the role of ET1 that has been implicated in the anxiogenic process. We found that infusing ET1 into the IL cortex increased anxiety-like behaviors. The ETAÂ receptor (ETAR) antagonist (BQ123) but not the ETBÂ receptor (ETBR) antagonist (BQ788) alleviated ET1-induced anxiety. ET1 had no effect on GABAergic neurotransmission or NMDA receptor (NMDAR)-mediated neurotransmission, but increased AMPA receptor (AMPAR)-mediated excitatory synaptic transmission. The changes in AMPAR-mediated excitatory postsynaptic currents were due to presynaptic mechanisms. Finally, we found that the AMPAR antagonists (CNQX) and BQ123 reversed ET1’s anxiogenic effect, with parallel and corresponding electrophysiological changes. Moreover, infusing CNQXâ€‰+â€‰BQ123 into the IL had no additional anxiolytic effect compared to CNQX treatment alone. www.getmetaz.xyz Altogether, our findings establish a previously unknown anxiogenic action of ET1 in the IL cortex. AMPAR-mediated glutamatergic neurotransmission may underlie the mechanism of ET1-ETAR signaling pathway in the regulation of anxiety.