Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.
Neuroscience
; 129(3): 733-42, 2004.
Article
em En
| MEDLINE
| ID: mdl-15541894
ABSTRACT
Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. Systemic administration of ultra-low doses of naltrexone (100 fg/kg-10 ng/kg) significantly potentiated the anticonvulsant effect of morphine at 0.5 mg/kg while higher degrees of opioid receptor antagonism blocked this effect. Moreover, inhibition of opioid-induced excitatory signaling by naltrexone (1 ng/kg) unmasked a strong anticonvulsant effect for very low doses of morphine (1 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of opioid receptor signaling can exert strong seizure-protective effects even at very low levels of opioid receptor activation. However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Convulsões
/
Morfina
/
Naltrexona
/
Antagonistas de Entorpecentes
/
Entorpecentes
Limite:
Animals
Idioma:
En
Revista:
Neuroscience
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Irã