Neurochemical and behavioural interactions between ibogaine and nicotine in the rat.
1. In vivo brain microdialysis has been employed to investigate the effects of ibogaine on nicotine-induced changes in dopamine overflow in the nucleus accumbens (NAc) of freely moving rats. The effects of the compound on locomotor responses to nicotine and behaviour in the elevated plus-maze were also examined. 2. No changes were observed in the dopamine overflow or the locomotor activity of the animals following the administration of ibogaine (40 mg kg-1, i.p.). However, ibogaine, administered 22 h earlier, significantly (P < 0.01) attenuated the increase in dopamine overflow but not the hyperlocomotion, evoked by nicotine. 3. In the elevated plus-maze test, significant reductions in the open:total runway entries in both saline-treated controls (P < 0.05) and nicotine-treated (P < 0.01) rats were obtained when the animals were tested 22 h after pretreatment with ibogaine (40 mg kg-1, i.p.). The total activity was significantly (P < 0.01) greater in the nicotine-treated rats but this response was not affected by ibogaine pretreatment. 4. Administration of ibogaine was associated with reductions in the tissue levels of 5-hydroxyindoleacetic acid (5-HIAA) in the NAc (P < 0.01) and striatum (P < 0.05) and an increase in the level of this metabolite in the medial prefrontal cortex (mPFC) (P < 0.01) while the levels of dopamine and 5-hydroxytryptamine (5-HT) in the mPFC were reduced (P < 0.05). The DOPAC/dopamine (P < 0.05) and 5-HIAA/5-HT (P < 0.01) ratios were significantly increased in the mPFC for at least 7 days after a single treatment with ibogaine. 5. Ibogaine attenuates the nicotine-induced increases in dopamine overflow in the NAc and may, therefore, inhibit the rewarding effects of this drug. However, the long lasting anxiogenesis induced by ibogaine warrant further investigation before its use could be recommended for smokers.
Benwell
M E
ME
Department of Pharmacology and Clinical Pharmacology, University of Dundee Medical School, Ninewells Hospital.
Holtom
P E
PE
Moran
R J
RJ
Balfour
D J
DJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D007050:Ibogaine; D006897:Hydroxyindoleacetic Acid; D009538:Nicotine; D004298:Dopamine