The effects of nociceptin on [3H]choline [3H](Ch) efflux from electrically-stimulated rat cortical, hippocampal and caudatal slices as well as from KCl-depolarized synaptosomes and tetrodotoxin-pretreated slices have been studied. The inhibition of electrically evoked [3H]Ch efflux by nociceptin (0.03-3 microM) was moderate (max -33%), more evident in the neocortex than in the hippocampus and was prevented by [Nphe1]NC(1-13)NH(2) 10 microM. This effect was absent in the caudate nucleus, in cortical synaptosomes and in tetrodotoxin-pretreated cortical slices. These data point to a distinct localization of NOP receptors in the different brain areas and to a prevailing inhibitory control by nociceptin on the cortical cholinergic input at pre-terminal level. However, the reported impairment of neocortical and hippocampal function by nociceptin may be referred to the inhibition not only of the cholinergic signal but also of other transmitters such as glutamate.