Neurochemical role of adenosine 3'', 5''-cyclic monophosphate and guanosine 3'', 5''-cyclic monophosphate and their relation to neurotransmitters; effect of tetrahydrocannabinols



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I Tetrahydrocannabinols: Both [delta]^8 THC and [delta]^9 THC depleted whole rat brain acetylcholine levels whereas [delta]^8 11-OH THC had no significant effect. [delta]^8 THC had no effect on choline acetyltransferase activity but did decrease AChE activity. Acetylcholine content of rat brain synaptosomal preparations was significantly decreased. Cyclic AMP is thought to control release of acetylcholine. [delta]^8 THC significantly increased cyclic AMP content in the rat midbrain while decreasing content in the cerebellum. Adenylate cyclase activity was decreased in both the cerebellum and midbrain by [delta]^8 THC; however, cyclic phosphodiesterase activity increased in the cerebellum and decreased in the midbrain. II Adenosine 3', 5'-Monophosphate; Dibutyryl cyclic AMP significantly increased locomotor activity in cannulated rats. Decreases in whole brain dopamine and norepinephrine levels were observed as well as an increase in serotonin and acetylcholine. No change in choline acetyltransferase activity was observed; however, decreased acetylcholinesterase activity was observed. Distribution of H^3 dibutyryl cyclic AMP was primarily confined to the rat kidney and liver. Little N^6 monobutyryl cyclic AMP was observed at 5" and subsequent time intervals; a large amount of a O^2' monobutyryl cyclic AMP mixture was observed at 5" and 15". Significant amounts of cyclic AMP were detected at 15" and subsequent time intervals. III Guanosine 3', 5'-Monophosphate: Intraventricular injections of dibutyryl cyclic GMP had no effect on whole brain dopamine, norepinephrine, and serotonin levels while decreasing acetylcholine content in the rat brain subcortical areas. Increases in acetylcholine levels were observed in the cerebral cortex-striatum. Choline acetyltransferase activity did not change in the subcortical areas whereas acetylcholinesterase activity increased; in the cerebral cortex-striatum, choline acetyltransferase and acetylcholinesterase activities decreased. Dibutyryl cyclic GMP did not affect H^3 dopamine release but did decrease uptake. An increase in tyrosine hydroxylase activity was observed.