Strain differences in responsiveness of norepinephrine-sensitive adenosine 3',5'-monophosphate-generating systems in rat brain slices after intraventricular administration of 6-hydroxydopamine.

The development of hyperresponsiveness in cyclic AMP-generating systems has been investigated in brain slices of Sprague-Dawley and F-344 rats following intraventricular administration of 6-hydroxydopamine. Hyperresponsiveness to adrenergic agonists in cerebral cortical slices of Sprague-Dawley rats pertained during the period 5-25 days after treatment with 6-hydroxydopamine. In contrast, hyperresponsiveness did not develop in cerebral cortical slices of F-344 rats. Reductions in norepinephrine levels of the cerebral cortex and hypothalamus following 6-hydroxydopamine treatment were comparable in the two rat strains. A hyperresponsiveness to norepinephrine and isoproterenol failed to develop in mesencephalic slices of either strain 12-14 days after treatment with 6-hydroxydopamine. The accumulation of cyclic AMP elicited by norepinephrine in cortical slices of F-344 rat is normally about 50% greater than the accumulation elicited in slices from Sprague-Dawley rats. However, after 6-hydroxydopamine treatment, there was no significant difference in the accumulations of cyclic AMP elicited in cortical slices from the two rat strains. These data indicate there may be a limit to the responsiveness of catecholamine-sensitive cyclic AMP generating systems which can develop following alterations in synaptic input.