Age-related electrophysiological changes in rat cerebellum

The spontaneous discharge of cerebellar Purkinje neurons was studied in 3-, 12-, 15-, and 20-month-old rats. Fluphenazine and haloperidol administered intraperitoneally produced a dose-dependent increase in the spontaneous discharge in 3-month-old animals, but were ineffective in 12-, 15- and 20-month-old rats. Intraperitoneal administration of amphetamine resulted in a dose-dependent decrease in spontaneous Purkinje neuron discharge in 3-month-old rats without affecting neurons from the older animals. Discrution of norepinephrine afferents by 6-OHDA or reserpine increased spontaneous discharge rate in 3-month-old animals. This treatment did not affect Purkinje neurons in 12-, 15- and 20-month-old rats. Local application of drug with the same multibarreled electrode revealed that neurons from older rats were significantly less sensitive to inhibition by norepinephrine than were Purkinje neurons from 3-month-old animals. Similar application of GABA did not reveal a differential sensitivity. For locus coeruleus activation to produce 50% inhibition in Purkinje neuron discharge, significantly higher stimulation currents were required in 15-month-old rats than in 3-month-old animals. Our results suggest a decreased postsynaptic sensitivity to norepinephrine in 12-, 15- and 20-month-old rats as compared to 3-month-old animals.