Medial prefrontal cortex is involved in the discriminative stimulus effects of nicotine in rats

Miyata, Hisatsugu; Ando, Kiyoshi; Yanagita, Tomoji

doi:10.1007/s002130051054

Cited by 15 publications

(16 citation statements)

References 7 publications

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“…Mecamylamine was used to probe for activity at central nicotinic acetylcholine receptors. Not surprisingly, mecamylamine blocked the discriminative stimulus effects of nicotine in the nicotine-trained rats, in agreement with earlier findings (Miyata et al, 1999;Rosecrans, 1989;Stolerman, 1988). Mecamylamine produced a small attenuation of the discriminative stimulus effects of methamphetamine in the methamphetamine-trained rats, but produced no effect on methamphetamine cross-substitution in the nicotine-trained rats.…”

Section: Mechanismssupporting

confidence: 91%

“…The discriminative stimulus effects of nicotine are primarily mediated by central nicotinic receptors, such that agonists at these receptors substitute in nicotine-trained rats, and mecamylamine blocks the discriminative stimulus effects of nicotine (Miyata et al, 1999;Rosecrans, 1989;Stolerman, 1988). Other receptors also contribute to the stimulus effects of nicotine, dopamine receptors producing the largest effect.…”

Section: Mechanism Of the Discriminative Stimulus Effects Of Nicotinementioning

confidence: 99%

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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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Section: Mechanismssupporting

confidence: 91%

Section: Mechanism Of the Discriminative Stimulus Effects Of Nicotinementioning

confidence: 99%

Nicotine and methamphetamine share discriminative stimulus effects

Gatch

Flores

Forster

2008

Drug and Alcohol Dependence

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“…This specificity allows researchers to explore and categorize the pharmacological properties of psychoactive compounds. For example, microinjections of nicotine into the medial prefrontal cortex and dorsal hippocampus evoke nicotineappropriate responding in rats trained to discriminate nicotine from saline via subcutaneous injections (Miyata et al, 1999;Shoaib and Stolerman, 1996). In contrast, microinjections of nicotine into the nucleus accumbens or the medial habenular nucleus did not result in nicotineappropriate responding.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

“…Such studies have determined that nicotine can alter glutamate release in several different areas of the brain, including the ventral tegmental area (Schilstrom et al, 1998(Schilstrom et al, , 2000Fu et al, 2000;Mansvelder and McGehee, 2000) the nucleus accumbens (Fu et al, 2000;Reid et al, 2000) the pre-frontal cortex (Toth et al, 1993;Vidal, 1994;Gioanni et al, 1999;) and the hippocampus (Gray et al, 1996;Radcliffe et al, 1999). These are areas thought to be involved in mediating the subjective (Rosecrans and Meltzer, 1981;Shoaib and Stolerman, 1992;Miyata et al, 1999) rewarding (Corrigall et al, 1994;Stolerman, 1996;Schroeder et al, 2001) and cognitive actions of nicotine (Stolerman, 1996;Levin et al, 1999).There is also growing evidence from behavioral models to indicate a role for glutamate in neurobiological mechanisms underlying the actions of nicotine. Investigators carrying out studies in rodents have reported that antagonists acting at N-methyl-D-aspartate (NMDA)-receptor sites can attenuate nicotine self-administration and the nicotine discriminative stimulus (Glick et al, 2001;Blokhina et al, 2005;Zakharova et al, 2005; but see also Wright et al, 2006) and the metabotropic GluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), has also been reported to be effective (Paterson et al, 2003;Paterson and Markou, 2005;Zakharova et al, 2005).…”

mentioning

confidence: 99%

Differential Involvement of Glutamatergic Mechanisms in the Cognitive and Subjective Effects of Smoking

Jackson

Nešić

Groombridge

et al. 2008

Neuropsychopharmacol

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There is growing preclinical evidence for the involvement of glutamate in the behavioral actions of nicotine. The aim of this study, was to investigate the role of N-methyl-D-aspartate (NMDA) receptors in the cognitive and subjective effects of smoking in humans. Sixty regular smokers took part in this double-blind placebo controlled study, that investigated the effect of the NMDA-antagonist memantine (40 mg) and the nicotinic-receptor antagonist mecamylamine (10 mg) on smoking-induced improvement in performance of a task of sustained attention and on smoking-induced changes in subjective effects and craving. Increases in subjective ratings of 'buzzed' following smoking were reversed by memantine, but not by mecamylamine. In contrast, improvement on a Rapid Visual Information Processing task by smoking was opposed by mecamylamine, but not by memantine. Smoking reduced craving for cigarettes, but neither drug altered this effect. Our results suggest that glutamatergic mechanisms may have differential involvement in the subjective and cognitive actions of smoking. Further investigations using different ligands are warranted to fully characterize the role of glutamate underlying the consequences of smoking behavior. Keywords: smoking; memantine; mecamylamine; subjective; craving; cognition INTRODUCTIONNicotine is known to have positively reinforcing, subjective and cognitive effects (Stolerman and Jarvis, 1995;Levin et al, 2006). In humans, some of the measurable subjective effects of nicotine include 'buzzed', 'dizzy', 'stimulated' (Perkins et al, 1999) while positive cognitive effects include improvements in attention (Wesnes and Warburton, 1984) and memory (Rusted et al, 1998). The neurobiological mechanisms underlying these actions of nicotine are complex, involving not only a direct action of nicotine at receptors for acetylcholine, but also changes in release of other neurotransmitters, such as dopamine and glutamate (Watkins et al, 2000).Neurochemical studies have demonstrated that, at concentrations achieved during smoking, nicotine can enhance the release and function of glutamate, through an action at presynaptic receptors (eg McGehee et al, 1995). Such studies have determined that nicotine can alter glutamate release in several different areas of the brain, including the ventral tegmental area (Schilstrom et al, 1998(Schilstrom et al, , 2000Fu et al, 2000;Mansvelder and McGehee, 2000) the nucleus accumbens (Fu et al, 2000;Reid et al, 2000) the pre-frontal cortex (Toth et al, 1993;Vidal, 1994;Gioanni et al, 1999;) and the hippocampus (Gray et al, 1996;Radcliffe et al, 1999). These are areas thought to be involved in mediating the subjective (Rosecrans and Meltzer, 1981;Shoaib and Stolerman, 1992;Miyata et al, 1999) rewarding (Corrigall et al, 1994;Stolerman, 1996;Schroeder et al, 2001) and cognitive actions of nicotine (Stolerman, 1996;Levin et al, 1999).There is also growing evidence from behavioral models to indicate a role for glutamate in neurobiological mechanisms underlying the actions of nicotine....

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Medial prefrontal cortex is involved in the discriminative stimulus effects of nicotine in rats

Abstract: Together with our previous study indicating that the nucleus accumbens and the ventral tegmental area are partially involved in the DS effects of nicotine, the present study suggests that mPFC is primarily involved in the DS effects of nicotine.

Cited by 15 publications

References 7 publications

Nicotine and methamphetamine share discriminative stimulus effects

Nicotine and methamphetamine share discriminative stimulus effects

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

Differential Involvement of Glutamatergic Mechanisms in the Cognitive and Subjective Effects of Smoking

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