Chronic marijuana smoke exposure in the rhesus monkey. IV: Neurochemical effects and comparison to acute and chronic exposure to delta-9-tetrahydrocannabinol (THC) in rats.
THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of the rat brain and muscarinic cholinergic (MCh) receptor binding was measured. For the acute in vivo study, rats were injected IP with vehicle, 1, 3, 10, or 30 mg THC/kg and sacrificed 2 h later. For the chronic study, rats were gavaged with vehicle or 10 or 20 mg THC/kg daily, 5 days/week for 90 days and sacrificed either 24 h or 2 months later. Rhesus monkeys were exposed to the smoke of a single 2.6% THC cigarette once a day, 2 or 7 days a week for 1 year. Approximately 7 months after the last exposure, animals were sacrificed by overdose with pentobarbital for neurochemical analyses. In vitro exposure to THC produced a dose-dependent inhibition of MCh receptor binding in several brain areas. This inhibition of MCh receptor binding, however, was also observed with two other nonpsychoactive derivatives of marijuana, cannabidiol and cannabinol. In the rat in vivo study, we found no significant changes in MCh or other neurotransmitter receptor binding in hippocampus, frontal cortex or caudate nucleus after acute or chronic exposure to THC. In the monkey brain, we found no alterations in the concentration of neurotransmitters in caudate nucleus, frontal cortex, hypothalamus or brain stem.(ABSTRACT TRUNCATED AT 250 WORDS)
Ali
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Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Newport
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GD
Scallet
A C
AC
Paule
M G
MG
Bailey
J R
JR
Slikker
W
W
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002185:Cannabidiol / Q000494:pharmacology; D002187:Cannabinol / Q000633:toxicity; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000097:blood / Q000633:toxicity*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008385:Marijuana Smoking / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D001679:Biogenic Amines; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D002185:Cannabidiol; D012701:Serotonin; D013759:Dronabinol; D002187:Cannabinol; D004298:Dopamine