부산대학교 도서관

Objective Marijuana and alcohol are most widely abused drugs among women of reproductive age. Neurocognitive deficits have been reported in children whose mothers used marijuana during pregnancy. Maternal consumption of ethanol is known to cause serious developmental deficits Methods Infant rats and mice received systemic injections of Δ9-tetrahydrocannabinol (THC; 1-10mg/kg) or the synthetic cannabinoid WIN 55,212-2 (1-10mg/kg), alone or in combination with subtoxic and toxic ethanol doses, and apoptotic neurodegeneration was studied in the brains Results Acute administration of THC (1-10mg/kg), the principal psychoactive cannabinoid of marijuana, markedly enhanced proapoptotic properties of ethanol in the neonatal rat brain. THC did not induce neurodegeneration when administered alone. Neuronal degeneration became disseminated and severe when THC was combined with a mildly intoxicating ethanol dose (3gm/kg), with the effect of this drug combination resembling the massive apoptotic death observed when administering ethanol alone at much higher doses. The detrimental effect of THC was mimicked by the synthetic cannabinoid WIN 55,212-2 (1-10mg/kg) and counteracted by the CB1 receptor antagonist SR141716A (0.4mg/kg). THC enhanced the proapoptotic effect of the GABAA agonist phenobarbital and the N-methyl- D-aspartate receptor antagonist dizocilpine. Interestingly, infant CB1 receptor knock-out mice were less susceptible to the neurotoxic effect of ethanol. Furthermore, the CB1 receptor antagonist SR141716A ameliorated neurotoxicity of ethanol Interpretation These observations indicate that CB1 receptor activation modulates GABAergic and glutamatergic neurotransmission and primes the developing brain to suffer apoptotic neuronal death. Ann Neurol 2007 [ABSTRACT FROM AUTHOR]