A specific harmaline-evoked increase in cerebellar 5′-nucleotidase activity

This study examines harmaline-induced changes in 5′-nucleotidase (5′-ND) activity in cerebellar fractions from rats with an intact inferior olive (IO) or prior destruction of the IO by 3-acetylpyridine (3-AP) intoxication. Harmaline markedly increased 5′-ND activity in the crude homogenate (P<0.05) and P2 fraction (P<0.001) of cerebella from rats with an intact IO. This increase was absent in the P1, P3 and S3 fractions and it was abolished by 3-AP olivectomy. It was also absent in basal ganglia P2 fractions. Since harmaline produces rhythmic complex spike discharges of Purkinje cells by activating IO neurons [4, 18], these data suggest that climbing fiber activation per se increases 5′-ND activity in the P2 fraction. This raises the possibility that a climbing fiber-induced local increase in 5′-ND activity at parallel fiber-Purkinje cell synapses results in a local increase in adenosine concentration. This may account for climbing fiber-evoked suppression of simple spike activity [12, 13, 28].