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On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures

Lutz, Beat

Biochemical pharmacology, 2004-11, Vol.68 (9), p.1691-1698 [Periódico revisado por pares]

New York, NY: Elsevier Inc

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  • Título:
    On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures
  • Autor: Lutz, Beat
  • Assuntos: Animals ; Biological and medical sciences ; Cannabinoid Receptor Modulators - physiology ; Cannabis - toxicity ; Endocannabinoids ; Epilepsy - metabolism ; Epilepsy - pathology ; Epileptic seizures ; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy ; Humans ; Medical sciences ; Models, Animal ; Nervous system (semeiology, syndromes) ; Neurology ; Neurons - physiology ; Neurotransmitters
  • É parte de: Biochemical pharmacology, 2004-11, Vol.68 (9), p.1691-1698
  • Descrição: Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB 1) receptors. Using mice lacking CB 1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB 1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB 1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB 1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.
  • Editor: New York, NY: Elsevier Inc
  • Idioma: Inglês
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