title: Pre- and post-conditioning treatment with an ultra-low dose of Δ9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage.
abstract: Preconditioning, a phenomenon where a minor noxious stimulus protects from a subsequent more severe insult, and post-conditioning, where the protective intervention is applied following the insult, offer new insight into the neuronal mechanism(s) of neuroprotection and may provide new strategies for the prevention and treatment of brain damage. We have previously reported that a single administration of an extremely low dose of Δ(9)-tetrahydrocannabinol (THC; the psychoactive ingredient of marijuana) to mice induced minor long-lasting cognitive deficits. In the present study we examined the possibility that such a low dose of THC will protect the mice from more severe cognitive deficits induced by the epileptogenic drug pentylenetetrazole (PTZ). THC (0.002 mg/kg, a dose that is 3-4 orders of magnitude lower than the doses that induce the conventional effects of THC) was administered 1-7 days before, or 1-3 days after the injection of PTZ (60 mg/kg). The consequences of this treatment were studied 3-7 weeks later by various behavioral tests that evaluated different aspects of memory and learning. We found that a single administration of THC either before or after PTZ abolished the PTZ-induced long-lasting cognitive deficits. Biochemical studies indicated a concomitant reduction in phosphorylated-ERK (extracellular signal-regulated kinase) in the cerebella of mice 7 weeks following the injection of THC. Our results suggest that a pre- or post-conditioning treatment with extremely low doses of THC, several days before or after brain injury, may provide safe and effective long-term neuroprotection.
authors.affiliation: The Adelson Center for Biology of Addictive Diseases and The Mauerberger Chair in Neuropharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel.
authors.forename: Fadi
authors.initials: F
authors.lastname: Assaf
authors.forename: Miriam
authors.initials: M
authors.lastname: Fishbein
authors.forename: Mikhal
authors.initials: M
authors.lastname: Gafni
authors.forename: Ora
authors.initials: O
authors.lastname: Keren
authors.forename: Yosef
authors.initials: Y
authors.lastname: Sarne
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018756:GABA Antagonists / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009483:Neuropsychological Tests; D010433:Pentylenetetrazole / Q000633:toxicity*; D011619:Psychotropic Drugs / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D013997:Time Factors
chemical_list: D018756:GABA Antagonists; D011619:Psychotropic Drugs; D013759:Dronabinol; D010433:Pentylenetetrazole