| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 4313790 | Behavioural Brain Research | 2011 | 8 Pages |
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 Δ9-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.
Research highlights► Pentylenetetrazole (PTZ) induces long lasting cognitive deficits in mice. ► An extremely low dose of tetrahydrocannabinol (THC) protects from PTZ-induced cognitive damage. ► An extremely low dose of THC evokes pre- and post-conditioning mechanisms that protect the brain. ► An extremely low dose of THC induces long lasting changes in ERK/MAPK activity.
