Topiramate does not alter nicotine or cocaine discrimination in rats

Foll, Bernard Le; Justinová, Zuzana; Wertheim, Carrie E.; Barnes, Chanel; Goldberg, Steven R.

doi:10.1097/fbp.0b013e3282f3cf84

Cited by 11 publications

(7 citation statements)

References 51 publications

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“…Rats were trained as described previously (e.g., (Justinova et al 2003; Le Foll et al 2008) under a discrete-trial schedule of food-pellet delivery to respond on one lever after an injection of a training dose of 0.4 mg/kg nicotine, 1 mg/kg methamphetamine or 10 mg/kg cocaine and on the other lever after an injection of 1 ml/kg of saline vehicle. Injections of nicotine were given subcutaneously 10 min before the start of the session.…”

Section: Methodsmentioning

confidence: 99%

Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats

et al. 2008

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Rationale Adenosine receptors are involved in cocaine and methamphetamine discrimination and exposure to caffeine can affect behavioral effects of nicotine in rats. Objectives Here we investigated the relative involvement of adenosine A 1 and A 2A receptors in nicotine, cocaine, and methamphetamine discrimination, before and/or during chronic caffeine exposure. Materials and methods The nonselective adenosine receptor antagonist caffeine, the A 1 -receptor antagonist cyclopentyltheophylline (CPT), and the A 2A -receptor antagonist MSX-3 were evaluated in rats trained to discriminate 0.4 mg/kg nicotine from saline under a fixed-ratio schedule of food delivery. Effects of adenosine receptor antagonists were then compared in rats discriminating nicotine, methamphetamine, or cocaine from saline during chronic caffeine exposure in their drinking water.Results Caffeine, CPT, and MSX-3 partially generalized to nicotine and shifted nicotine dose-response curves leftwards. During chronic caffeine exposure, however, all three ligands failed to generalize to nicotine and failed to shift nicotine dose-response curves. In previous experiments, CPT and MSX-3 partially generalized to methamphetamine and cocaine and shifted dose-response curves leftwards. In the present experiments, CPT neither generalized nor shifted dose-response curves for methamphetamine or cocaine during chronic caffeine exposure. However, MSX-3 partially generalized to both psychostimulants and shifted their dose-response curves leftwards. Caffeine partially generalized to cocaine, but not methamphetamine, and shifted both dose-response curves leftwards. Conclusions Both adenosine A 1 and A 2A receptors are capable of modulating the discriminative-stimulus effects of nicotine. Chronic caffeine exposure produces complete tolerance to both A 1 -and A 2A -mediated effects in nicotinetrained rats. In contrast, chronic caffeine exposure produces tolerance to adenosine A 1 -mediated, but not A 2A -mediated, effects in methamphetamine-and cocaine-trained rats.

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Section: Methodsmentioning

confidence: 99%

Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats

et al. 2008

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“…In addition it also inhibits voltage-gated Na + and Ca 2+ channels and activates GABA A receptors [62]. Even though topiramate does not alter cocaine discrimination in rats [63], it has been shown to reduce relapse in cocaine addicts [64]. In a 13-week, double-blind, placebocontrolled pilot trial, topiramate was titrated over eight weeks to a dose of 200mg/day.…”

Section: Ionotropic Receptors and Cocainementioning

confidence: 99%

Glutamate: The New Frontier in Pharmacotherapy for Cocaine Addiction

Uys¹,

LaLumiere²

2008

CNSNDDT

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Considerable research into the neurobiology of cocaine addiction has shed light on the role of glutamate. Findings from models of relapse to cocaine-seeking indicate that the glutamatergic system is critically involved, as glutamate levels in the nucleus accumbens increase during reinstatement and glutamate receptor activation is necessary for reinstatement to drug-seeking. Thus, it would seem beneficial to block the increased glutamate release, but full antagonists of ionotropic glutamate receptors produce undesirable side effects. Therefore, modulation of glutamatergic transmission would be advantageous and provide novel pharmacotherapeutic avenues. Pharmacotherapies have been developed that have the potential to modulate excessive glutamatergic transmission through ionotropic and metabotropic (mGluR) glutamate receptors. Compounds that modulate glutamatergic transmission through ionotropic glutamate receptors include the non-competitive N-methyl-D-aspartic acid antagonists, amantadine and memantine, and the partial N-methyl-D-aspartic acid agonist d-cycloserine. They have shown promise in preclinical models of cocaine addiction. The mGluR2/3 agonist LY379268 is effective in inhibiting cocaine seeking in preclinical animal models and could decrease stress-induced relapse due to its anxiolytic effects. Similarly, the mGluR1/5 antagonists, 2-methyl-6-(phenylethynyl)pyridine and 3-[2-methyl-4-thiazolyl)ethynyl]pyridine, have shown to be effective in preclinical models of cocaine addiction. The cysteine pro-drug, N-acetylcysteine, restores the inhibitory tone on presynaptic glutamate receptors and has been effective in reducing cue-induced craving and cocaine use in humans. Furthermore, anticonvulsants, such as topiramate or lamotrigine, have shown efficacy in treating cocaine dependence or reducing relapse in humans. Future pharmacotherapy may focus on manipulating signal transduction proteins and pathways, which include Homer/N-methyl-D-aspartic acid complexes, to provide effective treatment for cocaine addiction.

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“…Male Long-Evans rats (Charles River, Lachine, PQ, Canada) were used for all nicotine and food self-administration experiments, whereas male Sprague Dawley rats (Charles River, Wilmington, MA, USA) were used for discrimination studies to be consistent with previous studies (Le Goldberg, 2004, 2005;Le Foll et al, 2008). Animals were initially group housed in a humidity-and temperaturecontrolled (21-22 1C) vivarium on a 12-h reversed light/ dark cycle with access to ad libitum water and food.…”

Section: Subjects and Drugsmentioning

confidence: 99%

Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

Yan

Pushparaj

Strat

et al. 2011

Neuropsychopharmacol

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Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine self-administration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of food-seeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue- and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue- or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse.

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Topiramate does not alter nicotine or cocaine discrimination in rats

Cited by 11 publications

References 51 publications

Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats

Effects of chronic caffeine exposure on adenosinergic modulation of the discriminative-stimulus effects of nicotine, methamphetamine, and cocaine in rats

Glutamate: The New Frontier in Pharmacotherapy for Cocaine Addiction

Blockade of Dopamine D4 Receptors Attenuates Reinstatement of Extinguished Nicotine-Seeking Behavior in Rats

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