Long-term cognitive deficits induced by a single, extremely low dose of tetrahydrocannabinol (THC): behavioral, pharmacological and biochemical studies in mice.
We have previously reported that an injection of a single, extremely low dose (0.001 mg/kg) of delta 9-tetrahydrocannabinal (THC, the major psychoactive ingredient of marijuana) to mice deteriorated their performance in the Morris water maze test 3 weeks later. In the present study we verify our original findings and show that the long-term cognitive deficits that are induced in mice by a low dose of THC are even more pronounced in another behavioral test-the water T-maze. This effect was abolished by the CB1 receptor antagonist SR141716A, indicating the involvement of CB1 receptors. In an attempt to find a biochemical correlate to these deleterious consequences of such a low dose of THC, we investigated its effect on the activation of extracellular signal-regulated kinase (ERK1/2) in the cerebellum and hippocampus of the mice, two brain regions that were shown to participate in spatial learning. A significant increase in ERK1/2 phosphorylation was found in the cerebellum of mice 24 h following the injection of 0.001 mg/kg THC. These findings lead to further studies into the neuronal mechanisms underlying the long-term deleterious effects of THC and should be taken into consideration when evaluating the therapeutic benefits of cannabinoid drugs.
Senn
Roey
R
The Mauerberger Chair in Neuropharmacology, Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
Keren
Ora
O
Hefetz
Aya
A
Sarne
Yosef
Y
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D006213:Hallucinogens / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010880:Piperidines / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant
D006213:Hallucinogens; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D048049:Extracellular Signal-Regulated MAP Kinases; D000077285:Rimonabant