GABA facilitation by noradrenaline shows supersensitivity in cerebellum after 6-hydroxydopamine

Alterations of cerebellar Purkinje cell responses to microiontophoretically applied noradrenaline (NA) were studied in rats after the destruction of NA-containing afferents and terminals by 6-hydroxydopamine (6-OHDA). An enhanced efficacy of NA action after 6-OHDA treatment was indicated by a significant reduction in the mean iontophoretic current required for a threshold depressant response to NA. A potentiation of gamma aminobutyric acid (GABA)-mediated inhibition by administration of NA, similar to that previously observed in control animals, was also reliably elicited in 6-OHDA pretreated rats. In addition, Purkinje cells appeared to demonstrate an increase in sensitivity to such facilitating actions of NA, defined here as "modulatory supersensitivity". In contrast to the prolonged synergistic interactions between NA and GABA observed in control animals, however, the enhancement of the amino acid response in 6-OHDA treated animals did not persist beyond the period of NA ejection and converted instead to a period of rebound insensitivity to GABA action. These results provide electrophysiological evidence for the emergence of supersensitivity to NA action in cerebellum after the loss of noradrenergic input from locus coeruleus.