Neuronal localization of cannabinoid receptors and second messengers in mutant mouse cerebellum.

Four lines of mutant mice were used to investigate (1) the neuronal localization of cannabinoid receptors in the cerebellar molecular layer and (2) the anatomical association of these receptors with elements of the two second messenger systems in the brain. Two of the mutant lines--Purkinje cell degeneration and nervous--are selectively deficient in Purkinje cells; the other two--weaver and reeler--are deficient in granule cells. In the heterozygous mice, [3H]CP 55,940 binding to cannabinoid receptors was discretely and densely localized to the molecular layer, as was [3H]forskolin binding to adenylate cyclase and [3H]phorbol 12,13-dibutyrate binding to protein kinase C, a component of the phosphoinositide cycle. [3H]CP 55,940 and [3H]forskolin binding was selectively reduced in weaver and reeler homozygous mice but unchanged in Purkinje cell deficient and nervous homozygotes. No decreases in [3H]phorbol 12,13-dibutyrate binding were found in any of the homozygous mutants relative to the heterozygous littermates. The results suggest that cannabinoid receptors and adenylate cyclase are localized to granule cell axons in the molecular layer, whereas protein kinase C is equally distributed in parallel fibers and Purkinje cell dendrites.

Correlations between cis-platinum dosage and toxicity in a guinea pig model.

A guinea pig model was used to study correlations between cis-platinum dosage and level of hearing loss, hair cell loss in the cochlea. Other parameters measured included weight loss and serum urea, creatinine, and cis-platinum levels. The damage to the inner ear expressed as hearing loss and hair cell loss demonstrated a highly positive correlation with the dosage of cis-platinum, and only a moderately positive correlation with the cis-platinum serum levels. Weight loss correlated well with hearing loss.