DISTRIBUTION AND REGULATION OF CYCLIC NUCLEOTIDES LEVELS IN BRAIN, IN VIVO

Abstract

Levels of cyclic GMP in mouse cerebellum, in vivo were increased by oxotremorine, harmaline and amphetamine treatment and decreased by diazepam, atropine and reserpine. In addition, physical shaking and pentylenetetrazol seizures elevated cyclic GMP levels in cerebellum. Pentylenetetrazol also increased the levels of cyclic GMP in cerebral cortex, striatum, hippocampus and thalamus, whereas the other drugs and shaking only produced changes in cyclic GMP levels in some of these regions. The changes in cyclic GMP levels observed in regions of forebrain could not be predicted from the changes seen in cerebellum, i.e. some of the changes seen in forebrain were qualitatively similar, while others were qualitatively opposite to those observed in cerebellum. Cyclic AMP levels were more resistant than cyclic GMP to alterations by the above drugs and conditions; however levels of cyclic AMP were elevated by pentylenetetrazol seizures in all regions except striatum, and were slightly depressed by reserpine in hippocampus and thalamus, and by diazepam in striatum. These data demonstrate that drugs and conditions which are capable of altering cyclic GMP levels in cerebellum may not produce similar effects in other major regions of brain. The results of the present study support the hypothesis that changes in cyclic GMP levels in CNS reflect alterations of neuronal activity and may be independent of the processes leading to these alterations.