Magnesium deficiency reveals the neurotoxicity of delta-9-tetrahydrocannabinol (THC) low doses in rats.
In the present study, muricide behaviour (MB) was studied in Long Evans rats in various situations. The MB pattern of each experimental group was compared, in 6 successive assays 1 hr-delayed to that of natural killer rats (NK). The percentage of NK rats was 11% in the strain used. In the 11 mg THC/kg b.w. treated naive rats, a significant additional percentage of rats (59%) became muricidal. The durations of the 3 MB phases were significantly increased as a result of an increased aggressiveness in the 1st assay but returned progressively to NK values on the 6th assay, in parallel with the physiological elimination of THC. This result indicates a true killing training in those non killer rats that became muricidal under THC. A severe magnesium deficiency induced by a 50 ppm magnesium-deficient diet induced 100% MB whereas a 150 ppm magnesium deficiency did not induce additional MB. In the severe deficiency, the MB pattern was rather similar to that of NK with the exception of the attack on the living mouse which was doubled probably because of magnesium-induced hyperexcitability responsible for a lower attack efficiency. In both 50 but also 150 ppm magnesium-deficient rats, a single injection of THC at low doses (2, 4 or 8 mg THC/kg b.w.) which is without aggressive effect in control rats, induced a 100% MB, the pattern of which was all the more severe as the magnesium deficiency was important or the THC dose higher. The pattern showed an important decrease in the two first phases and a dramatic increase in the attack on the dead mouse, suggesting that the combination of both treatments provoked severe central damage with a compulsive killing behavior. Consequently, it appears that a magnesium deficiency, even a moderate one, may aggravate the neurotoxicity of THC at low doses and, reciprocally, that low doses of THC may reveal the potential neurotoxicity of a moderate magnesium deficiency.
Laboratoire de Pharmacologie, Faculté de Pharmacie, Paris XI, 92296 Châtenay Malabry.
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D000374:Aggression / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000633:toxicity*; D004334:Drug Administration Schedule; D008275:Magnesium Deficiency / Q000097:blood* / Q000523:psychology; D008297:Male; D051379:Mice; D051381:Rats; D020318:Rats, Long-Evans
D013759:Dronabinol