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Studies on noradrenergic supersensitivity of the cyclic AMP response in rat cerebral cortex Kallstrom, Elizabeth

Abstract

Intracerebral injections of the neurotoxin 6-OHDA into the dorsal bundle (DB) causes selective depletion of cortical noradrenaline (NA) stores. The cortical neurons may then develop supersensitivity to NA and this may be measurable by the level of cAMP accumulation. Seven days was chosen as a period of time from injection to the development of the supersensitive response, and ten weeks was taken as the long-term period to measure permanent effects of this treatment. At seven days there was a significant increase in maximal stimulation and a slight, but not significant, shift of the dose-response curve. The baseline values of cAMP remained unchanged. The effect of the cAMP system after ten weeks post-injection consisted of a significant shift of the dose-response curve to the left, corresponding to a lowering of K[sub D], and a significant increase in both baseline and maximal stimulation levels, or V[sub max], of cAMP. The very high responsiveness of the adenylate cyclase system during the end of the second post-natal week was characterized by higher baseline levels of cAMP and greater cAMP accumulation in response to all NA concentrations tested. However, there was no significant shift of the dose-response curve. Kindling had no effect on the NA-stimulated cAMP response, showing unchanged basal and maximal stimulation levels in both anterior and posterior cortical slices. These results are discussed in terms of our present knowledge of the role of cAMP as a component of the post-synaptic receptor complex.

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