Ibogaine and the dopaminergic response to nicotine
- 60 Downloads
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.
Key wordsNicotine Acute tolerance Ibogaine Dopamine Microdialysis In vivo Rat
Unable to display preview. Download preview PDF.
- 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: 1177–1185PubMedCrossRefGoogle Scholar
- Dhahir HI (1971) A comparative study of the toxicity of ibogaine and serotonin. Doctoral thesis, Ann Harbor, Mich., USA, University Microfilm International, 71-25-341Google 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 657:14–22PubMedCrossRefGoogle Scholar
- Lotsof HS (1985) Rapid method for interrupting the narcotic addiction syndrome. US Patent no. 4,499,096Google Scholar
- Lotsof HS (1986) Rapid method for interrupting the cocaine and amphetamine abuse syndrome. US Patent no. 4,587,243Google Scholar
- Lotsof HS (1989) Rapid method for attenuating the alcohol dependency syndrome. US Patent no. 4,857,523Google Scholar
- Lotsof HS (1991) Rapid method for interrupting or attenuating the nicotine/tobacco dependency syndrome. US Patent no. 5,026,697Google Scholar
- Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Orlando, Flo., USAGoogle 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 666:255–262PubMedCrossRefGoogle Scholar