In vivo effects of pentobarbital and halothane anesthesia on levels of adenosine 3', 5'-monophosphate and guanosine 3',5'-monophosphate in rat brain regions and pituitary

The effects of two general anesthetics, pentobarbital and halothane, on in vivo levels of cyclic AMP and cyclic GMP were examined in seventeen brain regions and the pituitary in the rat. Ventilation was controlled to produce normal values of arterial pH, pCO₂ and pO₂, to eliminate changes in cerebral perfusion and oxygen delivery which occur as a result of the respiratory depressant effect of these drugs. Arterial pressure was monitored and colonie temperature was maintained within normal limits. Pentobarbital was given as a single i.p. injection of 80mg/kg. Control animals received an equivalent volume of vehicle solution. Induction of halothane anesthesia was accomplished by placing the animals in a jar flushed with 3% halothane in air. After 3 min the animals received 2% halothane in air via a nose cone. Control animals for this experiment were placed in an air-filled jar. Experimental and control animals were killed by microwave irradiation 1 hr after the start of anesthesia. Both drugs decreased levels of cyclic GMP in virtually all regions. The largest changes occurred in the cerebellum, where cyclic GMP dropped to 7.4 per cent of control with pentobarbital and to 9.8 per cent of control following halothane. Levels of cyclic AMP significantly increased in the cerebellum, brainstem and hypothalamus after halothane, by 58, 49 and 65 per cent, respectively. Both pentobarbital and halothane markedly increased cyclic AMP levels in the pituitary (to 784 and 270 per cent of control values, respectively). These results show that halothane and pentobarbital, which modify synaptic transmission, selectively alter cyclic AMP and cyclic GMP levels in specific brain regions and the pituitary.