Diazepam attenuation of somatostatin-induced motor disturbances and neurotoxicity

Intracerebroventricular somatostatin administration to conscious rats results in a characteristic motor abnormality (barrel rotation), convulsions that are frequently fatal and destruction of cerebellar Purkinje cells. This study demonstrates that each of these manifestations of this neuropeptide can be attenuated by pretreatment with diazepam (Valium, 5 mg/kg, i.p.) but not in vehicle-pretreated controls. Specifically, the incidence of mortality was reduced from 5/12 controls to 2/20 diazepam-treated rats, the incidence of barrel rotation was reduced from 6/12 controls to 2/20 diazepam-treated rats and the incidence of Purkinje cell death was reduced from 4/4 examined controls to 4/13 diazepam-treated animals. Vehicle pretreated rats did not differ from untreated rats. Thus, in addition to blocking somatostatin-induced motor dysfunction and mortality, diazepam offers significant protection from central neuronal cell death in the cerebellar cortex.