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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 129 (1997), S. 249-256 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Acute tolerance ; Ibogaine ; Dopamine ; Microdialysis ; In vivo ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 128 (1996), S. 426-431 
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Mecamylamine ; Drug self-administration ; Smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A new oral model of nicotine self-administration in rats has been described. The model utilizes a two-lever operant procedure with rats having a choice between nicotine and water reinforcement. Most (16 of 20) rats exhibited reliable preferences for nicotine solutions equal to or less than 32 μg/ml; preferences were inversely related to the concentration of nicotine. Mecamylamine (0.25–5.0 mg/kg), a nicotinic antagonist, reduced preferences for a low nicotine concentration (4 μg/ml) and enhanced preferences for a high nicotine concentration (32 μg/ml). The relationship of nicotine concentration to nicotine preference appeared to be consistent with previous reports of nicotine self-administration using the intravenous route in rats as well as the respiratory route (i.e., smoking) in humans. The mecamylamine-induced changes in nicotine preference were consistent with its nicotinic antagonist action as well as with effects of mecamylamine reported in humans. This model should be useful in the preclinical assessment of new agents as potential therapies in smoking cessation programs.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Ibogaine ; 18-Methoxycoronaridine ; In vivo microdialysis ; Drug self-administration ; Smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two studies were conducted to assess, in vivo, potential anti-nicotinic effects of the iboga alkaloid ibogaine and its synthetic congener 18-methoxycoronaridine (18-MC). As previously demonstrated for ibogaine, using microdialysis, pretreatment (19 h beforehand) with 18-MC (40 mg/kg, IP) significantly attenuated nicotine-induced dopamine release in the nucleus accumbens of awake and freely moving rats. In an oral model of nicotine self-administration, both ibogaine and 18-MC decreased rats’ preferences for nicotine for at least 24 h. Acutely, during the first hour after administration, ibogaine depressed responding for water as well as for nicotine; however, during this same time, 18-MC reduced nicotine intake without affecting responding for water. The results suggest that 18-MC might be the prototype of a new treatment for smoking.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Keywords Ibogaine ; 18-Methoxycoronaridine ; Methamphetamine ; Locomotor activity ; Stereotypy ; Sensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The phenomenon of sensitization has been theoretically implicated in mediating various aspects of drug addiction. Recent dose-response studies demonstrated that pretreatment with the putative anti-addictive agent, ibogaine (IBO), and a synthetic iboga alkaloid congener, 18-methoxycoronaridine (18-MC), increase the potency of cocaine to elicit behavioral sensitization, an effect proposed to contribute, in part, to their ability to attenuate drug self-administration. Objectives: As abuse of the methylated amphetamine derivative, methamphetamine (METH), is a growing public health concern, the present study determined the interactions between IBO and 18-MC and the expression of METH-induced behavioral sensitization. Methods: The effects of pretreatment with 18-MC (40 mg/kg, IP, 19 h earlier) on the expression of METH-induced locomotion (0, 0.25, 0.5, 1 and 2 mg/kg, IP) and the effects of pretreatment with either IBO or 18-MC on the expression of METH-induced stereotypy (2 and 4 mg/kg, IP) were assessed in rats treated chronically with either METH (4 mg/kg daily for 7 days) or saline. Results: Compared to vehicle-pretreated controls, 18-MC produced an overall enhancement in METH-induced locomotion in rats treated chronically, but not acutely, with METH. In addition, both iboga agents increased the stereotypic response to METH. Conclusions: Iboga agents augment both the locomotor and stereotypic effects of METH in a manner consistent with previous reports for cocaine. Thus, it appears that iboga agents interact in a similar manner with the neural mechanisms mediating motor hyperactivity induced by the chronic administration of stimulant drugs.
    Type of Medium: Electronic Resource
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