CHANGES IN BRAIN LEVELS OF CYCLIC-NUCLEOTIDES AND GAMMA-AMINOBUTYRIC ACID IN BARBITURATE DEPENDENCE AND WITHDRAWAL

Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brains and exhibited increased sensitivity to audiogenic convulsions during the withdrawal period. Levels of γ-aminobutyric acid (GABA), glutamate, guanosine 3′,5′-monophosphate (cyclic GMP) and adenosine 3′,5′-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tendend to be reduced during barbital dependendence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicated a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal. © 1979.