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Ibogaine and the dopaminergic response to nicotine

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Abstract

There is increasing evidence that the rewarding effect of nicotine is mediated by the mesolimbic dopamine system. The first objective of this study was to examine the dopamine response to repeated IV infusions of nicotine. Using in vivo microdialysis in awake and freely moving male Sprague-Dawley rats, we demonstrated that IV nicotine infusions (0.16 mg/kg or 0.32 mg/kg per infusion) produced increases in extracellular dopamine levels that were dose- and infusion order-dependent. Acute tolerance was evidenced by the smaller dopamine response produced by a second infusion of nicotine, administered 1 h after the first one. Tolerance was reversible, since the dopamine response to a second infusion of nicotine was unchanged when the interval between the infusions was increased to 3 h. Ibogaine, an alkaloid found in Tabernanthe iboga, is claimed to decrease smoking and to have an anti-nicotinic action. The second objective of this study was to establish whether this claim has any neurochemical basis. Pretreatment with ibogaine (40 mg/kg, IP) 19 h prior to the first nicotine infusion (0.32 mg/kg per infusion) significantly attenuated the increase in extracellular dopamine levels induced by the nicotine infusions, suggesting that ibogaine may decrease the rewarding effect of nicotine.

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References

  • Banerjee S, Punzi JS, Kreilick K, Abood LG (1990) [3H]-Mecamylamine binding to rat brain membranes. Studies with mecamylamine and nicotine analogues. Biochem Pharmacol 40:2105–2110

    Article  PubMed  CAS  Google Scholar 

  • Benwell MEM, Balfour DJK (1992) The effects of acute and repeated nicotine treatment on nucleus accumbens dopamine and locomotor activity. Br J Pharmacol 105:849–856

    PubMed  CAS  Google Scholar 

  • Benwell MEM, Balfour DJK, Birrell CE (1995) Desensitization of the nicotine-induced mesolimbic dopamine responses during constant infusion with nicotine. Br J Pharmacol 114: 454–460

    PubMed  CAS  Google Scholar 

  • Benwell MEM, Holtom PE, Moran RJ, Balfour DJK (1996) Neurochemical and behavioural interactions between ibogaine and nicotine in the rat. Br J Pharmacol 117:743–749

    PubMed  CAS  Google Scholar 

  • Blomqvist O, Engel JA, Nissbrandt H, Söderpalm B (1993) The mesolimbic dopamine-activating properties of ethanol are antagonized by mecamylamine. Eur J Pharmacol 249:207–213

    Article  PubMed  CAS  Google Scholar 

  • Boksa P, Livett BG (1984) Desensitization to nicotinic cholinergic agonists and K+, agents that stimulate catecholamine secretion, in isolated adrenal chromaffin cells. J Neurochem 42: 607–617

    Article  PubMed  CAS  Google Scholar 

  • Brazell MP, Mitchell SN, Joseph MH, Gray JA (1990) Acute administration of nicotine increases the in vivo extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid and ascorbic acid preferentially in the nucleus accumbens of the rat: comparison with caudate-putamen. Neuropharmacology 29: 1177–1185

    Article  PubMed  CAS  Google Scholar 

  • Briggs CA, McKenna DG (1996) Effect of MK-801 at the human α7 nicotinic acetylcholine receptor. Neuropharmacology 35: 407–414

    Article  PubMed  CAS  Google Scholar 

  • Bullock AE, Barke KE, Schneider AS (1994) Nicotine tolerance in chromaffin cell cultures: acute and chronic exposure to smoking-related nicotine doses. J Neurochem 62:1863–1869

    PubMed  CAS  Google Scholar 

  • Bunn SJ, Dunkley PR (1991) Opioid inhibition of nicotine-induced 45Ca2(+)-uptake into cultured bovine adrenal medullary cells. Biochem Pharmacol 41:715 -722

    Article  PubMed  CAS  Google Scholar 

  • Cappendijk SLT, Dzoljic MR (1993) Inhibitory effects of ibogaine on cocaine self-administration in rats. Eur J Pharmacol 241: 261–265

    Article  PubMed  CAS  Google Scholar 

  • Carr LA, Rowell PP, Pierce WM Jr (1989) Effects of subchronic nicotine administration on central dopaminergic mechanisms in the rat. Neurochem Res 14:511–515

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Kokate TG, Donevan SD, Carroll I, Rogawski MA (1996) Ibogaine block of the NMDA receptor: in vitro and in vivo studies. Neuropharmacology 35:423–431

    Article  PubMed  CAS  Google Scholar 

  • Chu B, Anantharam V, Treistman SN (1995) Ethanol inhibition of recombinant heteromeric NMDA channels in the presence and absence of modulators. J Neurochem 65:140–148

    PubMed  CAS  Google Scholar 

  • Clarke PB, Pert A (1985) Autoradiographic evidence for nicotine receptors on nigrostriatal and mesolimbic dopaminergic neurons. Brain Res 348:355–358

    Article  PubMed  CAS  Google Scholar 

  • Clarke PB, Chaudieu I, El-Bizri H, Boksa P, Quik M, Esplin BA, Capek R (1994) The pharmacology of the nicotinic antagonist, chlorisondamine, investigated in rat brain and autonomic ganglion. Br J Pharmacol 111: 397–405

    PubMed  CAS  Google Scholar 

  • Corrigall WA, Coen KM (1991) Selective dopamine antagonists reduce nicotine self-administration. Psychopharmacology 104: 171–176

    Article  PubMed  CAS  Google Scholar 

  • Corrigall WA, Franklin KB, Coen KM, Clarke PB (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology 107:285–289

    Article  PubMed  CAS  Google Scholar 

  • Corrigall WA, Coen KM, Adamson KL (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area. Brain Res 653:278–284

    Article  PubMed  CAS  Google Scholar 

  • Damsma G, Day J, Fibiger HC (1989) Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens. Eur J Pharmacol 168:363–368

    Article  PubMed  CAS  Google Scholar 

  • Deecher DC, Teitler M, Soderlund DM, Bornmann WG, Kuehne ME, Glick SD (1992) Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Res 571:242–247

    Article  PubMed  CAS  Google Scholar 

  • Deneris ES, Connolly J, Rogers SW, Duvoisin R (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors (Review). Trends Pharmacol Sci 12: 34–40

    Article  PubMed  CAS  Google Scholar 

  • Dhahir HI (1971) A comparative study of the toxicity of ibogaine and serotonin. Doctoral thesis, Ann Harbor, Mich., USA, University Microfilm International, 71-25-341

    Google Scholar 

  • French ED, Mura A, Wang T (1993) MK-801, phencyclidine (PCP), and PCP-like drugs increase burst firing in rat A10 dopamine neurons: comparison to competitive NMDA antagonists. Synapse 13:108–116

    Article  PubMed  CAS  Google Scholar 

  • Gallagher CA, Hough LB, Keefner SM, Seyed-Mozaffari A, Archer S, Glick SD (1995) Identification and quantification of the indole alkaloid ibogaine in biological samples by gas chromatography-mass spectrometry. Biochem Pharmacol 49:73–79

    Article  PubMed  CAS  Google Scholar 

  • Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN (1991) Effects and aftereffects of ibogaine on morphine self-administration in rats. Eur J Pharmacol 195:341–345

    Article  PubMed  CAS  Google Scholar 

  • Glick SD, Rossman K, Wang S, Dong N, Keller RW Jr (1993) Local effects of ibogaine on extracellular levels of dopamine and its metabolites in nucleus accumbens and striatum: interactions with d-amphetamine. Brain Res 628:201–208

    Article  PubMed  CAS  Google Scholar 

  • Glick SD, Kuehne ME, Raucci J, Wilson TE, Larson D, Keller RW Jr, Carlson JN (1994) Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Brain Res 657:14–22

    Article  PubMed  CAS  Google Scholar 

  • Grady SR, Marks MJ, Collins AC (1994) Desensitization of nicotine-stimulated [3H]dopamine release from mouse striatal synaptosomes. J Neurochem 62:1390–1398

    Article  PubMed  CAS  Google Scholar 

  • Grenhoff J, Aston-Jones G, Svenson TH (1986) Nicotinic effects on the firing pattern of midbrain dopamine neurons. Acta Physiol Scand 128:351–358

    Article  PubMed  CAS  Google Scholar 

  • Gupta SK, Hwang SS, Causey D, Rolf CN, Gorsline J (1995) Comparison of the nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) and half-hourly cigarette smoking. J Clin Pharmacol 35:985–989

    PubMed  CAS  Google Scholar 

  • Hakan RL, Ksir C (1991) Acute tolerance to the locomotor stimulant effects of nicotine in the rat. Psychopharmacology 104: 386–390

    Article  PubMed  CAS  Google Scholar 

  • Hough LB, Pearl SM, Glick SD (1996) Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration. Life Sci 58:PL119–122

    Article  PubMed  CAS  Google Scholar 

  • Imperato A, Mulas A, Di Chiara G (1986) Nicotine preferentially stimulates dopamine in the limbic system of freely moving rats. Eur J Pharmacol 132:337–338

    Article  PubMed  CAS  Google Scholar 

  • Javitt DC, Zukin SR (1989) Biexponential kinetics of [3H]MK-801 binding: evidence for access to closed and open N-methyl-d-aspartate receptor channels. Mol Pharmacol 35:387–393

    PubMed  CAS  Google Scholar 

  • Kiba H, Jayaraman A (1994) Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation. Mol Brain Res 23:1–13

    Article  PubMed  CAS  Google Scholar 

  • Kumakura K, Karoum F, Guidotti A, Costa E (1980) Modulation of nicotinic receptors by opiate receptor agonists in cultured adrenal chromaffin cells. Nature 283:489–492

    Article  PubMed  CAS  Google Scholar 

  • Lapin EP, Maker HS, Bhardwaj A (1995) Ethanol enhancement of the motor-stimulating effect of nicotine in the rat. Alcohol 12: 217–220

    Article  PubMed  CAS  Google Scholar 

  • Lester RAJ, Dani J A (1995) Acetylcholine receptor desensitization induced by nicotine in rat medial habenula neurons. J Neurophysiol 74:195–206

    PubMed  CAS  Google Scholar 

  • Lotsof HS (1985) Rapid method for interrupting the narcotic addiction syndrome. US Patent no. 4,499,096

    Google Scholar 

  • Lotsof HS (1986) Rapid method for interrupting the cocaine and amphetamine abuse syndrome. US Patent no. 4,587,243

  • Lotsof HS (1989) Rapid method for attenuating the alcohol dependency syndrome. US Patent no. 4,857,523

  • Lotsof HS (1991) Rapid method for interrupting or attenuating the nicotine/tobacco dependency syndrome. US Patent no. 5,026,697

  • Maisonneuve IM, Keller RW Jr, Glick SD (1991) Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. Eur J Pharmacol 199: 35–42

    Article  PubMed  CAS  Google Scholar 

  • Maisonneuve IM, Glick SD (1992) Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior. Eur J Pharmacol 212:263–266

    Article  PubMed  CAS  Google Scholar 

  • Maisonneuve IM, Keller RW Jr, Glick SD (1992) Interactions of ibogaine and D-amphetamine: in vivo microdialysis and motor behavior in rats. Brain Res 579:87–92

    Article  PubMed  CAS  Google Scholar 

  • Marley PD (1988) Desensitization of the nicotinic secretory response of adrenal chromaffin cells. Trends Pharmacol Sci 9:102–107

    Article  PubMed  CAS  Google Scholar 

  • Mash DC, Staley JK, Baumann MH, Rothman RB, Hearn WL (1995a) Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin. Life Sci 57:PL45-PL50

    Article  PubMed  CAS  Google Scholar 

  • Mash DC, Staley JK, Pablo JP, Holohean AM, Hackman JC, Davidoff RA (1995b) Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex. Neurosci Lett 192:53–56

    Article  PubMed  CAS  Google Scholar 

  • Mifsud JC, Hernandez L, Hoebel BG (1989) Nicotine infused into the nucleus accumbens increases synaptic dopamine as measured by in vivo microdialysis. Brain Res 478:365–367

    Article  PubMed  CAS  Google Scholar 

  • McGehee DS, Heath MJ, Gelber S, Devay P, Role LW (1995) Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors (see comments). Science 269:1692–1696

    Article  PubMed  CAS  Google Scholar 

  • Miller RP, Rotenberg KS, Adir J (1977) Effect of dose on the pharmacokinetics of intravenous nicotine in the rat. Drug Metab Dispos 5:436–443

    PubMed  CAS  Google Scholar 

  • Nisell M, Nomikos GG, Svensson TH (1994) Infusion of nicotine in the ventral tegmental area or the nucleus accumbens of the rat differentially affects accumbal dopamine release. Pharmacol Toxicol 75:348–352

    Article  PubMed  CAS  Google Scholar 

  • Ochoa EL, Chattopadhyay A, McNamee MG (1989) Desensitization of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cell Mol Neurobiol 9:141–178

    Article  PubMed  CAS  Google Scholar 

  • O’Dell TJ, Christensen BN (1988) Mecamylamine is a selective noncompetitive antagonist of N-methyl-d-aspartate- and aspartate-induced currents in horizontal cells dissociated from the catfish retina. Neurosci Lett 94:93–98

    Article  PubMed  CAS  Google Scholar 

  • Ohno M, Watanabe S (1995) Persistent increase in dopamine release following activation of metabotropic glutamate receptors in the rat nucleus accumbens. Neurosci Lett 200:113–116

    Article  PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Orlando, Flo., USA

    Google Scholar 

  • Pearl SM, Herrick-Davis K, Teitler M, Glick SD (1995) Radioligand-binding study of noribogaine, a likely metabolite of ibogaine. Brain Res 675:342–344

    Article  PubMed  CAS  Google Scholar 

  • Plowchalk DR, Andersen ME, deBethizy JD (1992) A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. Toxicol Appl Pharmacol 116: 177–188

    Article  PubMed  CAS  Google Scholar 

  • Popik P, Layer RT, Skolnick P (1994) The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex. Psychopharmacology 114: 672–674

    Article  PubMed  CAS  Google Scholar 

  • Ramoa AS, Alkondon M, Aracava Y, Irons J, Lunt GG, Deshpande SS, Wonnacott S, Aronstam RS, Albuquerque EX (1990) The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels. J Pharmacol Exp Ther 254:71–82

    PubMed  CAS  Google Scholar 

  • Sweetnam PM, Lancaster J, Snowman A, Collins JL, Perschke S, Bauer C, Ferkany J (1995) Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine’s putative anti-addictive activity. Psychopharmacology 118: 369–376

    Article  PubMed  CAS  Google Scholar 

  • Taber MT, Fibiger HC (1995) Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: modulation by metabotropic glutamate receptors. J Neurosci 15:3896–3904

    PubMed  CAS  Google Scholar 

  • Varanda WA, Aracava Y, Sherby SM, VanMeter WG, Eldefrawi ME, Albuquerque EX (1985) The acetylcholine receptor of the neuromuscular junction recognizes mecamylamine as a noncompetitive antagonist. Mol Pharmacol 28:128–137

    PubMed  CAS  Google Scholar 

  • Wang T, O’Connor WT, Ungerstedt U, French ED (1994) N-methyl-d-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area: in vivo microdialysis and in vitro electrophysiological studies. Brain Res 666:255–262

    Article  PubMed  CAS  Google Scholar 

  • Yoshida M, Yokoo H, Tanaka T, Mizoguchi K, Emoto H, Ishii H, Tanaka M (1993) Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid agonist and nicotine as examined with in vivo microdialysis. Brain Res 624:277–280

    Article  PubMed  CAS  Google Scholar 

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Maisonneuve, I.M., Glick, S.D., Mann, G.L. et al. Ibogaine and the dopaminergic response to nicotine. Psychopharmacology 129, 249–256 (1997). https://doi.org/10.1007/s002130050187

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