The effect of ibogaine on kappa-opioid- and 5-HT3-induced changes in stimulation-evoked dopamine release in vitro from striatum of C57BL/6By mice.
Ibogaine is an indole alkaloid that has been suggested to have potential efficacy for interrupting dependency on stimulant drugs. The kappa-opioid and serotonin 5-HT3 systems may be involved in the action of ibogaine, related to their modulation of dopaminergic transmission. The kappa-opioid agonist U 62066 attenuated the in vitro stimulation-evoked efflux of tritium label from striatal tissue prelabeled with [3H]dopamine. In mice pretreated with ibogaine.HCI (40 mg/kg IP given 2 h prior or 2 x 40 mg/kg and animals killed 18 h later), the inhibitory effect of U 62066 on stimulation-evoked release of tritium was eliminated. The 5-HT3 agonist phenylbiguanide had a biphasic effect on stimulation-evoked release of tritium; at 10(-6) M phenylbiguanide, stimulation-evoked release was attenuated. At 10(-5) M the basal outflow of tritium was increased. Ibogaine pretreatment had no effect on basal or stimulation-evoked release in the presence of 10(-6) M phenylbiguanide, but increased the stimulation-evoked outflow of tritium in the presence of 10(-5) M phenylbiguanide. Cocaine (10(-6) M), a dopamine uptake blocker, increased the electrically-evoked release of dopamine; ibogaine pretreatment did not affect the enhanced electrically-induced release of [3H]dopamine by in vitro cocaine. The effects of ibogaine on the kappa-opioid and 5-HT3 receptors, located presynaptically on striatal dopamine terminals, modulating dopamine release may partly underlie its putative antiaddictive properties.
Sershen
H
H
Nathan S. Kline Institute, Center for Neurochemistry, Orangeburg, NY 10962, USA.
Hashim
A
A
Lajtha
A
A
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D007050:Ibogaine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*
D001645:Biguanides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D011985:Receptors, Serotonin; D007050:Ibogaine; D003042:Cocaine; C051272:spiradoline; D004298:Dopamine; C008846:phenyl biguanide