Roberto and Siggins (2006) found that nociceptin did not significantly alter the resting membrane potential, input resistance, or spike amplitude, in accord with the results reported by others in CeA (Meis and Pape 1998) and for other brain regions (Ikeda et al. 1997; Madamba et al. 1999; Tallent et al. 2001). However, nociceptin dose-dependently reduced GABAA IPSCs. This inhibition of GABAergic transmission was reversible on washout (Roberto and Siggins 2006). Nociceptin also concomitantly increased the PPF of IPSCs, and decreased the frequency of mIPSCs, suggesting decreased GABA release. Thus, nociceptin decreases GABAergic transmission by reducing GABA release at CeA synapses (Roberto and Siggins 2006). Interestingly, nociceptin applied before EtOH completely prevented the EtOH-induced enhancement of GABAergic transmission in CeA. On the other hand, EtOH alone significantly increased both the evoked IPSCs and mIPSC frequencies, and decreased the PPF ratio; nociceptin in the presence of EtOH completely reversed these EtOH effects opposing the EtOH increase of GABA release (Roberto and Siggins 2006). These investigators also found that the nociceptin-induced decrease of GABAergic transmission was larger in EtOH-dependent rats and might reflect neuroadaptations associated with EtOH dependence.
