Role of training dose in discrimination of nicotine and related compounds by rats

Stolerman, I. P.; Garcha, H. S.; Pratt, Julian; Kumar, Ramesh

doi:10.1007/bf00555223

Cited by 158 publications

(118 citation statements)

References 15 publications

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“…The ED 50 for amphetamine (0.281 mg/kg) was also within the range described in operant drug discrimination experiments employing a 1 mg/kg training dose (0.26 mg/kg and 0.40 mg/kg (Young et al, 1998)]. Also similar to previous findings using operant drug discrimination procedures, CDP did not substitute for any of the stimulants that we trained as drug features (eg Stolerman et al, 1984), nor did any stimulant substitute for CDP (eg Gauvin et al, 1994). Finally, nicotine and amphetamine partially substituted for one another, although only 0.2 mg/kg nicotine statistically differed from saline controls (for similar findings in operant drug discrimination studies, see Bardo et al, 1997;Chance et al, 1977;Li and McMillan, 2003;Mansbach et al, 1998;Stolerman, 1989).…”

Section: Discussionsupporting

confidence: 84%

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED 50 s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED 50 ¼ 15.45 mg/kg) and amphetamine (ED 50 ¼ 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

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Section: Discussionsupporting

confidence: 84%

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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“…Each of these 3 training doses has served as a discriminative stimulus for rats in a 2-lever operant drug discrimination task (Chance et al, 1977, Desai et al, 2003, Gasior et al, 1999, Morrison and Stephenson, 1969and Stolerman et al, 1997. In this task, completion of a response requirement on one lever results in reinforcement, whereas responses on the other lever result in no reinforcement (Gasior et al, 2000, Gasior et al, 2002, Morrison and Stephenson, 1969, Stolerman, 1989and Stolerman et al, 1984. On intermixed vehicle sessions, responding on the opposite lever is reinforced.…”

Section: Discussionmentioning

confidence: 99%

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Murray

Bevins

2007

European Journal of Pharmacology

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“…The case for asymmetry should perhaps not be overstated, as earlier studies have reported both full and partial substitution by dopamine compounds in nicotine-trained subjects (Desai et al, 1999;Gasior et al, 1999;Mansbach et al, 1998) (Wiley et al, 2002;Young and Glennon, 2002) and both full and partial substitution by nicotine in other dopaminergic psychostimulants (de la Garza and Johanson, 1983;1985;Desai et al, 1999;Desai et al, 2003). It is important to note that the degree of cross-substitution between methamphetamine and nicotine could be determined by training dose, as different patterns of stimulus control can be seen between groups trained to discriminate a high or a low dose of drug (Koek and Slangen, 1982;Stolerman et al, 1984). This effect is more pronounced when there are differences in mechanism or degree of efficacy between the compounds being tested, as is the case for methamphetamine and nicotine.…”

Section: Cross-substitutionmentioning

confidence: 91%

Nicotine and methamphetamine share discriminative stimulus effects

Gatch

Flores

Forster

2008

Drug and Alcohol Dependence

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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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Role of training dose in discrimination of nicotine and related compounds by rats

Cited by 158 publications

References 15 publications

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

Nicotine and methamphetamine share discriminative stimulus effects

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