Alterations in turnover and endogenous levels of norepinephrine in cerebral cortex following electrical stimulation and acute axotomy of cerebral noradrenergic pathways

Abstract

The turnover and endogenous levels of norepinephrine (NE) in the cerebral cortex (including the hippocampus) were measured after acute axotomy and electrical stimulation of the ascending NE pathways originating from the locus coeruleus. Acute unilateral axotomy of the dorsal NE pathway induces a small increase of NE in the cerebral cortex (ipsilateral vs. contralateral) and a decreased metabolism of NE (as estimated after synthesis inhibition by α-methyl-p-tyrosine). Electrical stimulation (20 Hz) of the locus coeruleus leads to a rapid decrease of NE levels to about 60% of the controls and new steady state levels of NE were reached in 7.5 min. After terminating the stimulation, the levels of NE in the cerebral cortex returned to normal within about 30 min. Electrical stimulation (20 Hz) of the locus coeruleus, after inhibition of NE synthesis, results in a biphasic decline of NE. The first phase is ended in about 2 min (30% decrease) after stimulation, the second phase persists for at least 30 min. The rate of decline of levels of NE in the cerebral cortex in the first phase is about 10 times higher than the rate of decline of the second phase. These results indicate that the level of NE in the cerebral cortex is in part dependent on the nerve impulse flow through the adrenergic fibres and are in favor of the concept of a multiple storage form for NE in the central nerve terminals.