Effects of stimulatory and depressant drugs on cyclic guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate levels in mouse brain.

Cyclic GMP levels were dose-dependently increased by excitatory drugs such as picrotoxin, pentetrazol, oxotremorine and harmaline in mouse cerebellum and medial forebrain (parts of the cortex, hippocampus, hypothalamus, thalamus, striatum and midbrain) in vivo. Cyclic AMP levels remained unchanged under these conditions. Pretreatment with diazepam completely abolished the effect of picrotoxin and harmaline and significantly reduced the effects of pentetrazol and oxotremorine on cyclic GMP levels, but the tremor due to harmaline and oxotremorine was not blocked. Pretreatment with pentobarbital also prevented or strongly reduced changes in cyclic GMP levels elicited by excitatory drugs without abolishing the tremorigenic effects of harmaline and oxotremorine. Pretreatment with atropine was only effective in blocking cyclic GMP rise and tremor induced by oxotremorine and picrotoxin. Since pentobarbital and diazepam also decreased cyclic GMP levels in a dose-dependent manner in brains of control animals, the changes in cyclic GMP levels observed after administration of excitatory drugs appear to be related to the arousal reaction of the central nervous system.