The effects of chronic oral administration of barbital on cerebellar cyclic GMP.

Female Sprague-Dawley rats received increasing dosages of barbital mixed with ground LabBlox for 7 weeks. At the end of this period, the rats were given doses of barbital acutely, and the effects of this treatment on levels of cyclic guanosine monophosphate (cGMP) in the cerebellum were determined. Chronic administration of barbital resulted in a slight depression of cGMP compared to control values. The acute injections of barbital produced a dramatic, dose-related decrease in levels of cerebellar cGMP in both control (C) and barbital-dependent (BD) animals. This depression of cGMP is of particular interest because the barbital-dependent animals had considerably higher levels of serum barbital than matched controls. The overall effect of chronic administration of barbital was right shift in the dose-response curve for levels of cGMP following acute injections of barbital. No differences in motor activity were noted between the dependent and control animals. It is believed that these results indicate that a high degree of tolerance is developed in the cGMP system of the cerebellum after chronic oral administration of barbital. Further investigation of this neurochemical parameter may provide useful information in the study of mechanisms mediating the dependence and the abstinence syndrome to barbiturates.