Activity-induced elevation of cerebellar cyclic GMP occurs in the absence of climbing fiber pathways.

The inferior olivary nuclei (ION) of Sprague-Dawley rats were chemically lesioned with 3-acetylpyridine (3-AP), and the completeness verified by the lack of retrograde labeling of the ION following the injection of horseradish peroxidase (HRP) into the cerebellum. The effects of locomotor activity or of immobilization on cerebellar cyclic guanosine monophosphate (cGMP) levels were determined in control saline-treated and experimental, 3-AP-treated rats. Three subgroups of rats from both the control and the experimental groups of rats were required to swim for 60 s, immobilized for 60 s or unmanipulated before being killed by microwave irradiation, and the cerebella were collected for cGMP determination. There was no statistically significant difference in cGMP levels between immobilized and unmanipulated rats in either the experimental or control groups. Pretreatment with 3-AP reduced cerebellar cGMP levels in both the immobilized and the unmanipulated rats to 50% of those observed in the comparably treated groups of saline-treated controls. When compared to the corresponding group of unmanipulated rats, locomotor activity induced a significantly greater elevation of cerebellar cGMP in the experimental animals than in the controls (P less than 0.05). These results indicate that while inputs from the ION to the cerebellar Purkinje cells are probably important in maintaining the normal levels of cGMP seen in inactive rats, the locomotor-induced elevation of this parameter occurs in the absence of climbing fibers (from ION). The mechanisms responsible for the greater activity-induced elevation of cGMP levels seen in rats receiving 3-AP over control rats are discussed.