Halothane effect on cGMP and control of motor activity in mouse cerebellum

The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane.