Alpha-1 adrenoreceptor-mediated increase in ACh release in brain slices during morphine tolerance

Abstract: Norepinephrine, clonidine, and phenylephrine increased the electrically evoked release of endogenous acetylcholine in cortical slices taken from morphine‐tolerant guinea pigs. This effect was α1adrenoreceptor mediated and was opposite to the α2‐adrenoreceptor‐mediated inhibition of acetylcholine release, normally elicited by norepinephrine and clonidine. In the presence of prazosin, clonidine recovered its normal inhibitory properties, suggesting that morphine tolerance induced the appearance of an α1adrenoreceptor‐mediated response that overshadowed, but did not cancel, the still present α2‐adrenoreceptor inhibitory control. The attempt to prove the presence of α‐adrenoreceptors on the nerve endings by testing the effect of norepinephrine in synaptosomal preparations (preloaded with [3H]choline and de‐polarized with KCL and veratridine) was unsuccessful. Therefore the problem of the exact location of this excitatory input remains to be solved. These results confirm previous ...