Effect of chronic morphine treatment on alpha(2)-adrenoceptor mediated autoinhibition of transmitter release from sympathetic varicosities of the mouse vas deferens

1 The effect of chronic morphine treatment (CMT) on sympathetic innervation of the mouse vas deferens and on alpha (2)-adrenoceptor mediated autoinhib ition has been examined using intracellular recording of excitatory junctio n potentials (EJPs) and histochemistry. 2 In chronically saline treated (CST) preparations. morphine (1 muM) and th e alpha (2)-adrenoceptor agonist (clonidine, 1 muM) decreased the mean ampl itude of EJPs evoked with 0.03 Hz stimulation by 81+/-8% (n=16) and 92+/-6% (n=7) respectively. In CMT preparations, morphine (1 muM) and clonidine (1 muM) decreased mean EJP amplitude by 68+/-8% (n = 7) and 79+/-8% (n = 7) r espectively. 3 When stimulating the sympathetic axons at 0.03 Hz. the mean EJP amplitude recorded from smooth muscles acutely withdrawn from CMT was four times gre ater than for CST smooth muscles (40.7+/-3.8 mV, n = 7 compared with 9.9+/- 0.3 mV, n = 7). 4 Part of the increase in mean EJP amplitude following CMT was produced by a 31% increase in the density of sympathetic axons and varicosities innerva ting the smooth muscle. 5 Results from the present study indicate that the effectiveness of alpha ( 2)-adrenocrptor mediated autoinhibition is only slightly reduced in CMT pre parations. Most of the cross tolerance which develops between morphine, clo nidine and alpha (2)-adrenoceptor mediated autoinhibition occurs as a conse quence of increased efficacy of neuromuscular transmission which is produce d by an increase in the probability of transmitter release and an increase in the density of sympathetic innervation.