MECHANISM FOR THE INCREASE OF BRAIN 5-HYDROXY-TRYPTAMINE AND 5-HYDROXYINDOLEACETIC ACID FOLLOWING Δ9-TETRAHYDROCANNABINOL ADMINISTRATION TO RATS

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Abstract
Wistar King A rats were treated i.p. with 10 mg/kg of THC [.DELTA.9-tetrahydrocannabinol], followed by 20 mg/kg of TBZ [tetrabenazine] s.c. 60 min later. The animals were sacrificed 90 min later and brain 5-HT [5-hydroxytryptamine, serotonin] and 5-HIAA [5-hydroxyindoleacetic acid] were estimated. Treatment with TBZ alone resulted in remarkable increase in brain 5-HIAA and decrease in 5-HT. TBZ-induced increase in 5-HIAA was not influenced by pretreatment with THC but a decrease in 5-HT by TBZ was significantly inhibited. In order to determine the possible mechanism for the increase in brain 5-HIAA after THC administration, an experiment on Sprague-Dawley rats was designed to observe if an accumulation of brain 5-HIAA following probenecid administration would be influenced by THC treatment. When Sprague-Dawley rats were treated with 200 mg/kg of probenecid (i.p.) and were sacrificed 60 min later, the brain level of 5-HIAA increased significantly. Simultaneous treatment with 20 mg/kg of THC (i.p.) and 200 mg/kg of probenecid (i.p.) resulted in an increase in brain level of 5-HIAA but this increase was almost equal in magnitude to that observed in animals treated with probenecid alone. The increase in 5-HIAA by probenecid was not influenced by a simultaneous administration of THC. The increase in 5-HIAA after THC administration was apparently not due to an increase in 5-HT synthesis nor an increase in the degradation of 5-HT due to activation of monoamine oxidase, but rather to the same mechanism as that of probenecid, i.e., the blockade of transport of 5-HIAA from the brain.