Abstract:These results suggest that high bupropion doses decrease responding nonspecifically; whereas low bupropion doses selectively increase responding for nicotine. The increase in nicotine self-administration is likely due to inhibition of dopamine and norepinephrine transporters, combined with inhibition of nAChRs.
“…However, since there were no differences in the effect of pretreatment with 10 mg/kg of methylphenidate between rats self-administering either nicotine unit dose, it is possible that high doses of stimulants can alter nicotine self-administration nonspecifically. While the precise reason(s) for this biphasic pattern of results is unknown, Rauhut et al (2003) found similar biphasic dose effects of acute bupropion or methamphetamine pretreatment on nicotine self-administration in rats. Prada and Goldberg (1985) also reported that caffeine pretreatment increased nicotine self-administration in squirrel monkeys at low doses (3-10 mg/kg), while higher doses (60-100 mg/kg) decreased response rates.…”
Section: Discussionmentioning
confidence: 78%
“…As these mechanisms would suggest, it has been shown that coadministration of methylphenidate augments nicotineinduced increases in extracellular dopamine content in the NAcc (Gerasimov et al, 2000a, b), suggesting that the interactive effects of these drugs on mesolimbic dopamine transmission underlies the behavioral interactions noted in the present study. Regarding self-administration specifically, blockade of central dopamine receptors reduces nicotine self-administration (Corrigall and Coen, 1991;Corrigall et al, 1992), whereas administration of monoamine oxidase inhibitors or the dopamine reuptake inhibitor bupropion increases nicotine self-administration (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). One caveat to this interpretation is that methylphenidate and bupropion are relatively nonselective inhibitors of the norepinephrine and dopamine transporters Han and Gu, 2006).…”
Section: Discussionmentioning
confidence: 99%
“…In a microdialysis study using rats, coadministration of cocaine with nicotine was shown to produce an additive increase in extracellular dopamine levels in the nucleus accumbens (NAcc) relative to administration of nicotine alone (Gerasimov et al, 2000a, b). Similarly, behavioral studies have shown that administration of indirect dopamine agonists, such as monoamine oxidase inhibitors (which prevent intracellular metabolism of dopamine) or bupropion (a dopamine reuptake inhibitor), increase nicotine self-administration in rats (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). Thus, it is possible that stimulant drugs increase nicotine self-administration, at least in part, by augmenting nicotine-induced increases in extracellular dopamine levels in the NAcc.…”
Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.
“…However, since there were no differences in the effect of pretreatment with 10 mg/kg of methylphenidate between rats self-administering either nicotine unit dose, it is possible that high doses of stimulants can alter nicotine self-administration nonspecifically. While the precise reason(s) for this biphasic pattern of results is unknown, Rauhut et al (2003) found similar biphasic dose effects of acute bupropion or methamphetamine pretreatment on nicotine self-administration in rats. Prada and Goldberg (1985) also reported that caffeine pretreatment increased nicotine self-administration in squirrel monkeys at low doses (3-10 mg/kg), while higher doses (60-100 mg/kg) decreased response rates.…”
Section: Discussionmentioning
confidence: 78%
“…As these mechanisms would suggest, it has been shown that coadministration of methylphenidate augments nicotineinduced increases in extracellular dopamine content in the NAcc (Gerasimov et al, 2000a, b), suggesting that the interactive effects of these drugs on mesolimbic dopamine transmission underlies the behavioral interactions noted in the present study. Regarding self-administration specifically, blockade of central dopamine receptors reduces nicotine self-administration (Corrigall and Coen, 1991;Corrigall et al, 1992), whereas administration of monoamine oxidase inhibitors or the dopamine reuptake inhibitor bupropion increases nicotine self-administration (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). One caveat to this interpretation is that methylphenidate and bupropion are relatively nonselective inhibitors of the norepinephrine and dopamine transporters Han and Gu, 2006).…”
Section: Discussionmentioning
confidence: 99%
“…In a microdialysis study using rats, coadministration of cocaine with nicotine was shown to produce an additive increase in extracellular dopamine levels in the nucleus accumbens (NAcc) relative to administration of nicotine alone (Gerasimov et al, 2000a, b). Similarly, behavioral studies have shown that administration of indirect dopamine agonists, such as monoamine oxidase inhibitors (which prevent intracellular metabolism of dopamine) or bupropion (a dopamine reuptake inhibitor), increase nicotine self-administration in rats (Guillem et al, 2005(Guillem et al, , 2006Rauhut et al, 2003). Thus, it is possible that stimulant drugs increase nicotine self-administration, at least in part, by augmenting nicotine-induced increases in extracellular dopamine levels in the NAcc.…”
Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.
“…Nicotine attenuated reinstatement of methamphetamine self-administration (Hiranita et al, 2004;Hiranita et al, 2006), and mecamylamine decreased methamphetamine self-administration in rats (Glick et al, 2002). In rats trained to self-administer nicotine, bupropion and methamphetamine increased selfadministration of low doses of nicotine and decreased self-administration of high doses of nicotine (Rauhut et al, 2003). These findings indicate a definite interaction between the two compounds; in particular, that the two compounds produce cross-sensitization implies a similar mechanism.…”
Section: Interactions Between Methamphetamine and Nicotinementioning
confidence: 73%
“…The most obvious possibility is that nicotinic acetylcholine receptors are located on dopaminergic neurons in the ventral tegmental area which are important in regulating neuronal activity of these dopaminergic neurons (Mameli-Engvall et al, 2006;Ungless and Cragg, 2006). Administration of nicotine modulates dopamine release (Quarta et al, 2006;Wonnacott et al, 2005), and is known to alter behaviors controlled by these dopaminergic pathways including locomotor behavior (Kuribara, 1999;Suemaru et al, 1993) and self-administration of abused compounds, including both nicotine and methamphetamine (Glick et al, 2002;Hiranita et al, 2004;Hiranita et al, 2006;Rauhut et al, 2003). The failure of mecamylamine to block the cross-substitution of methamphetamine in nicotine-trained rats may be related to the finding that perfusion of mecamylamine into the nucleus accumbens did not alter dopamine levels in the ventral tegmental area or the nucleus accumbens (Rahman and McBride, 2002).…”
Background-Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo.Methods-The purpose of this study was to characterize the extent to which these two compounds produce similar discriminative stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally-acting nicotinic antagonist (mecamylamine) to block the discriminative stimulus effects of methamphetamine and nicotine were also tested.Results-Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the discriminative stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the discriminative stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect.Conclusions-These results indicate that nicotine and methamphetamine share discriminative stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.
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