Pretreatment with delta 1-tetrahydrocannabinol and psychoactive drugs: effects on uptake of biogenic amines and on behavior.
Injection of delta 1-tetrahydrocannabinol (THC) into mice increased the uptake into brain synaptosomes of radioactive DA, NE, 5-HT and GABA, with the effect on GABA being the greatest; uptake of leucine was not stimulated, indicating that THC does not facilitate the transport of amino acids in general. The effect of THC was stereospecific because pretreatment with the non-psychoactive isomer, (+) delta 6-THC had no effect on uptake of DA into cortical synaptosomes. The effect on DA uptake was correlated with psychoactive potency. THC enhanced uptake more than did SP-111 (a water soluble ester of THC but less potent than THC) and much more than cannabidiol (a non-psychoactive ingredient of marijuana). THC increased the uptake of DA into striatal synaptosomes but much less than into cortical synaptosomes. The enhancing effect of THC on uptake in cortex showed tolerance after chronic (1 week) treatment with THC. Catecholaminergic receptor antagonists (chlorpromazine, propranolol), like THC, stimulated the uptake of DA or NE into cortical synaptosomer. In contrast, pretreatment with MAO (pargyline) or uptake (tricyclic antidepressants) inhibitors, or with amphetamine, decreased uptake. Thus THC does not inhibit MAO uptake, or stimulate the release of catecholamines but may interact with a receptor. The notion of a THC--receptor interaction is supported by behavioral experiments.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001679:Biogenic Amines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001679:Biogenic Amines; D011619:Psychotropic Drugs; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D013759:Dronabinol; D007930:Leucine; D001058:Apomorphine; D004298:Dopamine; D009638:Norepinephrine