Demonstration of neurochemical tolerance following chronic barbital treatment.

Control rats (C) and rats rendered barbital dependent (BD) by the consumption of barbital chronically in their food for 6 weeks were treated with saline or 1 of 3 acute dosages of barbital 16 minutes before killing. Cyclic guanosine monophosphate (cGMP) levels and circulating levels of barbital were measured. Significantly higher circulating levels of barbital were required to produce a comparable suppression of cerebellar cGMP in the BD as opposed to the C rats. These data provide evidence for the development of tolerance to barbital in the cerebellar cGMP system during chronic barbital treatment. When barbital was abruptly withdrawn from BD rats, a profound elevation of cerebellar cGMP was observed to precede and outlast behavioral manifestations of barbital abstinence. Further understanding of the withdrawal induced aberrations in the mechanisms regulating cerebellar cGMP may give insight into the pathways involved in the manifestation of the barbital abstinence syndrome.