Presynaptic alpha 2-adrenoceptor subsensitivity in the morphine-withdrawn mouse vas deferens

The present study compares the inhibitory effects of clonidine and histamine on electrically evoked twitches in vasa deferentia isolated from morphine-dependent and 'withdrawn' mice. The electrically evoked twitches of preparations removed from 'withdrawn' mice were increased by 45% over control responses. A reduction in the maximal twitch inhibition induced by clonidine was detected in both groups. However, only preparations isolated from 'withdrawn' mice showed subsensitivity to clonidine as characterized by a rightward displacement of the concentration-effect curve (1.5-fold at the IC50 level). In contrast, morphine treatment or withdrawal did not affect the sensitivity of the preparation to the twitch inhibition induced by histamine (0.1-10 microM). Higher concentrations of histamine (30-100 microM) induced a greater degree of twitch inhibition in vasa deferentia isolated from morphine-treated and 'withdrawn' mice. These results demonstrate that in addition to the previously reported increased responsiveness to noradrenaline, vasa deferentia isolated from mice withdrawn from morphine display subsensitivity to the presynaptically mediated effects of clonidine. This withdrawal reaction from opiates observed in the mouse vas deferens seems to be very similar to that reported for noradrenergic transmission within the CNS.