Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors.
Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a noncompetitive NMDA antagonist. The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. Jumping, a major behavioral expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK-801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine-dependent animals treated with IBO or MK-801. This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.
Leal
Mirna Bainy
MB
Faculdade de Farmácia, Pontifícia Universidade Católica do Rio Grande do Sul, Rua da República 580/306, Cep: 90050-320, Porto Alegre, RS, Brazil. mirnabl@pucrs.br
Michelin
Kátia
K
Souza
Diogo Onofre
DO
Elisabetsky
Elaine
E
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D007050:Ibogaine / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D007050:Ibogaine; D016291:Dizocilpine Maleate; D009020:Morphine