ADAPTIVE MECHANISMS OF THE NORADRENERGIC CYCLIC AMP GENERATING SYSTEM IN THE LIMBIC FOREBRAIN OF THE RAT: ADAPTATION TO PERSISTENT CHANGES IN THE AVAILABILITY OF NOREPINEPHRINE (NE)^1,²

Abstract

Abstract— The noradrenergic cyclic AMP generating system in slices of the limbic forebrain of rats displays characteristics which are compatible with those of a central NE receptor. The cyclic AMP response to a K max concentration of NE (concentration of NE which elicits maximal increase in the level of cyclic AMP) is significantly enhanced in slices from reserpinized animals, although the K a value of NE (concentration of NE eliciting half‐maximum response) was not significantly changed. Chemosympathectomy with 6‐hydroxydopamine (6‐OHDA) significantly enhanced the activity of the system to NE and isoproterenol but not to adenosine and reduced the K a value for NE. The changes in the reactivity of the cyclic AMP generating system following 6‐OHDA administration appear to be related to a decrease in the availability of NE and not to that of other neurotransmitters as protection by desipramine (DMI) of noradrenergic neurons against the neurotoxic action of 6‐OHDA prevented the development of supersensitivity to NE. Conversely, and independent of the actual concentration of NE in brain tissue, a persistent increase in the availability of NE caused by prolonged MAO inhibition lead to a marked decrease in the reactivity of the cyclic AMP generating system. The results provide further evidence for a regulatory mechanism in the CNS involving the noradrenergic receptor that adapts its sensitivity to NE in a manner inversely related to the degree of its stimulation by the catecholamine.