Differential neurochemistry and temporal pattern in rats treated orally with delta9-tetrahydrocannabinol for periods up to six months
| Autor: | Harris Rosenkrantz, Irwin A. Heyman, Monique C. Braude, Yugal K. Luthra |
|---|---|
| Rok vydání: | 1975 |
| Předmět: |
Male
medicine.medical_specialty Cerebellum Ataxia Time Factors Aché Administration Oral Nerve Tissue Proteins Biology Hyperkinesis Toxicology Neurochemical Seizures Internal medicine medicine Animals Humans Dronabinol Cannabis Pharmacology Brain Chemistry Behavior Animal Cerebrum Neurotoxicity RNA Brain Catatonia medicine.disease language.human_language Enzyme assay Stimulation Chemical Rats Aggression medicine.anatomical_structure Endocrinology Depression Chemical language biology.protein Acetylcholinesterase Female medicine.symptom |
| Zdroj: | Toxicology and applied pharmacology. 32(2) |
| ISSN: | 0041-008X |
| Popis: | Groups of male and female Fischer rats were treated orally with Δ9-THC doses of 2, 10, or 50 mg/kg for 28, 90, and 180 days. Another group of rats treated for 180 days was studied after a 30-day recovery period. The lowest dose employed in the present study corresponded to Δ9-THC content of one high-grade marihuana cigarette and the intermediate dose simulated the Δ9-THC content of one hashish cigarette. In the first 10 days CNS-depression, incoordination, ataxia and passivity, poikilothermia, and hypopnea occurred to which tolerance developed. During days 10–20, irritability, hypersensitivity, hyperactivity, and aggression predominated. Peaks of fighting occurred between days 20–100 among 60% of the animals at higher doses. Tremors and clonic convulsions appeared after day 70 in 50% of the animals at 50 mg/kg and 12% at 10 mg/kg. Tolerance developed to CNS-stimulation, fighting, and neurotoxicity. At necropsy, different portions of the brain were used to prepare 10% ( w v ) homogenates which were analyzed for protein, RNA, and AChE activity. After 28 treatments, only cerebellar RNA increased approximately 16% in both sexes on the high dose. RNA was unchanged after 90 treatments although there was a parallel decline in RNA and protein in various parts of female brain. An 11–21% decrease in RNA was found in cerebral portions of males receiving 50 mg/kg for 180 days. A dose-related fall in protein and RNA in cerebral and cerebellar homogenates from both sexes resulted in no alteration of RNA concentration after a 30-day recovery interval. AChE activity was depressed 17–34% in female cerebellum after 28 treatments and continued treatment for 90 days initiated slight decrements in enzyme activity in various portions of male brain at the high dose. Prolonged treatment for 180 days elevated AChE activity 19–70% in all portions of brain in the males in a nearly dose-related fashion. On the other hand, AChE activity diminished 8–48% in the female. During the recovery period, enzyme activity increased 11–43% in cerebrum and 19–78% in cerebellum for both sexes. Neurochemical alterations were in part sex-related and coincided with behavioral changes associated with cumulative toxicity. Although tolerance is known to develop to most clinical abnormalities, some neurochemical changes persisted after cessation of treatment. |
| Databáze: | OpenAIRE |
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