Effects of noradrenaline depletion on adrenergic and muscarinic cholinergic receptors in the cerebral cortex, hippocampus, and cerebellum

The effects of noradrenaline depletion on α- and β-adrenergic and muscarinic cholinergic receptors in the cerebral cortex, hippocampus, and cerebellum of Wistar rats were studied. Noradrenaline depletion was obtained either by chemical (6-hydroxydopamine) lesions of the locus cerulet's or by chronic reserpine treatment. Two weeks after locus ceruleus lesions and 10 days after chronic reserpine treatment, the rats were killed and the cerebral cortex, hippocampus, and cerebellum dissected. A small portion of each tissue was assayed for noradrenaline, to assess the success of locus ceruleus lesions or reserpine treatment, and the remainder was used to measure the specific binding of tritiated α- and β-adrenergic and muscarinic cholinergic receptor ligands to particulate fractions of these tissues. The effect of noradrenaline depletion on isoproterenol-induced cyclic AMP generation in cerebellar slices was also studied. Noradrenaline depletion whether by locus ceruleus lesion or chronic reserpine treatment induced reproducible and significant increases in the binding to β-adrenergic receptors in the cerebral cortex and hippocampus. Scatchard analyses revealed that this increased binding was due to an increased density of β-adrenergic receptor binding sites. In the cerebellum, however, noradrenaline depletion did not result in an increase in β-adrenergic receptor binding nor in isoproterenol-induced cyclic AMP generation. Noradrenaline depletion did not cause significant changes in the binding characteristics of α-adrenergic or muscarinic cholinergic receptors in any of the three regions of the brain that were studied.