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.
The effect on renal function, and the plasma and urinary disposition, of digoxin-specific antibody fragments (DSFab), were studied using the rat as an experimental model. After 24h, DSFab (2 mg kg-1, i.v.) caused decreases in urine volume and creatinine clearance of 34 and 33%, respectively, when measured in the same rats. However, only the creatinine clearance was significantly changed when compared with a separate saline-treated control group. Plasma and urinary creatinine concentrations were unaffected by DSFab treatment. Since creatinine clearance approximates to glomerular filtration rate (GFR), it appears that a dose of DSFab equivalent to about one-fifth of the usual clinical dose, causes a reduction in GFR of about one-third. In patients undergoing digitalis therapy, a degree of renal impairment is common and it is possible that this may be exacerbated by treatment with DSFab. DSFab had an elimination half-life of 178 min, an apparent volume of distribution (Vd) of 106 mL kg-1 and a plasma clearance of 0.42 mL kg-1 min-1. If it is assumed that the plasma volume of a rat is approximately 35 mL kg-1, the measured Vd suggests appreciable penetration of DSFab into the extracellular fluid at this dose. Seventy-two hours after injection, only 7.6% of the administered dose of DSFab was found in the urine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.