1 In vivo brain microdialysis has been employed to investigate the effects of ibogaine on nicotineinduced 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-', 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 salinetreated 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-', 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.
1 The present study compared high anity neurotensin (NT) binding in rat brain following acute or chronic treatment with the classical antipsychotic, haloperidol, and the newer antipsychotic drugs, clozapine and zotepine. 2 Drugs were given orally, as an acute treatment (1 dose) or chronically (21 day dosing) and binding to the NT high anity receptor was examined in three brain regions; striatum, nucleus accumbens/olfactory tubercle and frontal cortex. 3 Acute dosing with either vehicle, haloperidol, clozapine or zotepine produced no signi®cant changes in NT binding from controls (naõÈ ve rats). 4 Chronic (21 day) dosing resulted in an increase in the K D and B max of high anity receptors in the striatum following haloperidol, but not clozapine, zotepine or vehicles. In contrast, the newer antipsychotics, clozapine and zotepine but not haloperidol or vehicles, signi®cantly altered NT binding in the nucleus accumbens/olfactory tubercle by decreasing the K D and B max . 5 Further dierentiation between the two newer antipsychotic drugs occurred in the frontal cortex. Clozapine had no signi®cant eect on NT binding, whereas zotepine signi®cantly reduced the K D of the high anity receptor with no alteration in B max . 6 The antipsychotic drugs tested did not interact directly with the NT high anity receptor. Therefore, they must be acting indirectly via an alternative receptor mechanism to alter NT high anity binding. In accordance with previously reported NT/dopamine receptor interactions, this would suggest cross-talk between these systems. 7 Overall, these data demonstrate that chronic, but not acute, administration of antipsychotic drugs alters NT binding in the rat brain. In addition, anatomical dierences in NT binding arise according to the antipsychotic drug under test. This may be predictive of drug side-eect pro®le, antipsychotic ecacy or atypicality.
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