NEUROCHEMICAL AND BEHAVIORAL INTERACTIONS BETWEEN IBOGAINE AND NICOTINE IN THE RAT

1 In vivo brain microdialysis has been employed to investigate the eff ects of ibogaine on nicotine-induced changes in dopamine overflow in t he nucleus accumbens (NAc) of freely moving rats. The effects of the c ompound on locomotor responses to nicotine and behaviour in the elevat ed plus-maze were also examined.2 No changes were observed in the dopa mine overflow or the locomotor activity of the animals following the a dministration of ibogaine (40 mg kg(-1), i.p.). However, ibogaine, adm inistered 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 nico tine-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 ra ts but this response was not affected by ibogaine pretreatment. 4 Admi nistration of ibogaine was associated with reductions in the tissue le vels of 5-hydroxyindoleacetic acid (5-HIAA) in the NAc (P<0.01) and st riatum (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 signific antly increased in the mPFC for at least 7 days after a single treatme nt with ibogaine. 5 Ibogaine attenuates the nicotine-induced increases in dopamine overflow in the NAc and may, therefore, inhibit the rewar ding effects of this drug. However, the long lasting anxiogenesis indu ced by ibogaine warrant further investigation before its use could be recommended for smokers.