Availability of calcium for noradrenergic contraction of the mouse isolated vas deferens is not altered during tolerance to and dependence on morphine.

1. The present study assesses the influence of tolerance to and dependence on morphine on the availability of Ca2+ for contraction of the mouse isolated vas deferens induced by noradrenaline (NA). 2. Reducing Ca2+ content in the bathing solution from 2.5 to 1.2 or 0.6 mM significantly reduced the magnitude of NA-induced contractions. This effect was similar in preparations obtained from control and tolerant/dependent mice (P greater than 0.05 at any Ca2+ concentration). 3. Omission of Ca2+ from the bathing solution caused a rapid and similar loss of responsiveness to a maximally effective concentration of NA (300 microM) in both groups (t1/2 less than 3 min, P greater than 0.05). 4. Vasa deferentia obtained from control and tolerant/dependent mice were equally susceptible to non-competitive antagonism of NA-induced contraction by verapamil (3 to 30 microM; pD2' values of 5.50 and 5.26, respectively, (P greater than 0.05 at any concentration of verapamil). 5. Preparations from tolerant/dependent mice displayed significant supersensitivity to NA, the magnitude of which was not influenced by modifying the Ca2+ concentration in the bathing medium (2.6- and 1.7-fold in 0.6 and 2.5 mM Ca2+, respectively, P less than 0.05). 6. I conclude that tolerance to and dependence on morphine are not associated with changes in the availability of Ca2+ for NA-induced contractions of the mouse vas deferens.