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Journal of Neuroscience, Vol 5, 2359-2364, Copyright © 1985 by Society for Neuroscience
Opiate- and alpha 2-adrenoceptor-induced hyperpolarizations of locus ceruleus neurons in brain slices: reversal by cyclic adenosine 3':5'- monophosphate analogues
R Andrade and GK Aghajanian
The purpose of this study was to investigate the ionic and second messenger
mechanisms underlying the hyperpolarizations induced by the selective alpha
2-adrenoceptor agonist clonidine and the opiate agonist morphine in the
locus ceruleus. Intracellular recordings were carried out in rat brain
slices, and drugs at known concentrations were administered in the
perfusate. The cyclic adenosine 3':5'-monophosphate (cAMP) analogues
8-bromo-cAMP and dibutyryl cAMP, while not altering basal activity,
reversed the hyperpolarizations induced by clonidine or morphine. In
contrast, administration of the parent compound adenosine failed to affect
these responses. These results are consistent with previous biochemical
studies suggesting that alpha 2-adrenergic and opiate agonists might signal
their actions by reducing intracellular cAMP levels. Under manual voltage
clamp, both clonidine and morphine elicited outward currents. The algebraic
sum of the individual currents elicited by morphine and clonidine
significantly exceeded the actual current elicited by their
co-administration. This nonadditivity, as well as the observation that cAMP
analogues reverse the morphine- and clonidine-induced hyperpolarizations,
suggests that these compounds hyperpolarize locus ceruleus neurons through
a shared ionic mechanism the activation of which might be signaled by a
decrease in intracellular cAMP.
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