Effects of blockade of α4β2 and α7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats

Liu, Xiu

doi:10.1017/s1461145713000874

Cited by 27 publications

(22 citation statements)

References 106 publications

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“…Responses on the inactive lever were recorded but had no programmed consequences. All rats received 25 daily sessions since our previous work has demonstrated successful establishment of stable nicotine self-administration under such a training schedule (Liu et al, 2008; Liu, 2014). Rats met the criterion of ≥ 10 infusions per session with ≤ 20% variation for at least three consecutive sessions.…”

Section: Methodsmentioning

confidence: 99%

“…The criterion for extinction was three consecutive sessions, in which the number of responses per session was ≤ 20% of the responses averaged across the last three sessions of the self-administration training phase. All of the rats underwent 10 extinction test sessions because our previous studies showed that nicotine-maintained responding was typically extinguished within 7–10 sessions (Liu et al, 2008; Liu, 2010; Liu, 2014). …”

Section: Methodsmentioning

confidence: 99%

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Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats

et al. 2017

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Rationale Increasing clinical evidence suggests that menthol, a significant flavoring additive in tobacco products, may contribute to smoking and nicotine dependence. Relapse to smoking behavior presents a formidable challenge for the treatment of tobacco addiction. An unresolved issue is whether the mentholation of tobacco products precipitates relapse to tobacco use in abstinent smokers. Objectives The present study examined the effects of menthol on the perseverance and relapse of nicotine-seeking behavior in rats. Methods Male Sprague-Dawley rats were trained to press a lever for intravenous nicotine self-administration (0.03 mg/kg/infusion) under a fixed-ratio 5 schedule of reinforcement. Each nicotine infusion was signaled by the presentation of a sensory stimulus that was established as a discrete nicotine-conditioned cue. Five minutes prior to the sessions, the rats received an intraperitoneal injection of menthol (0.1 mg/kg) or vehicle. In the subsequent extinction test sessions, nicotine was unavailable with or without menthol and/or the nicotine-conditioned cue. The reinstatement tests were performed the following day after the extinction criterion was met. Menthol was also tested on food-seeking responses. In a subset of nicotine-trained rats, a TRPM8 antagonist RQ-00203078 was given prior to menthol administration. Results Continued administration of menthol sustained responses on the previously active and nicotine-reinforced lever in the extinction tests. The re-administration of menthol after extinction reinstated active lever responses. In both the extinction and reinstatement tests, a combination of pre-session menthol administration and cue re-presentation during the session produced a more robust behavioral effect than either menthol or the cue alone. No such effects of menthol was observed in food trained rats. RQ-00203078 did not change menthol effect on nicotine seeking. Conclusion These data demonstrated that menthol specifically sustained and reinstated nicotine-seeking behavior and this effect was independent of TRPM8 activity. These findings suggest that menthol in most tobacco products, even not menthol-labeled, may contribute to the perseverance of and relapse to tobacco-seeking behavior.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats

et al. 2017

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“…Although the neuropharmacology that underlies relapse to smoking is not fully understood, animal models of relapse or reinstatement of nicotine seeking have been developed for investigating potential pharmacotherapies that may attenuate reinstatement following relapse triggers [7–9]. Interestingly, the first-line smoking cessation drug varenicline was shown not to block cue-induced relapse to nicotine seeking in rats [10], although it attenuated reinstatement when cues were combined with a nicotine priming injection [11] or a longer pretreatment time was used [12].…”

Section: Introductionmentioning

confidence: 99%

The α3β4 nAChR partial agonist AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats

Yuan

Malagon

Yasuda

et al. 2017

Behavioural Brain Research

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The strong reinforcing effects of nicotine and the negative symptoms such as anxiety experienced during a quit attempt often lead to relapse and low success rates for smoking cessation. Treatments that not only block the reinforcing effects of nicotine but also attenuate the motivation to relapse are needed to improve cessation rates. Recent genetic and preclinical studies have highlighted the involvement of the α3, β4, and α5 nicotinic acetylcholine receptor (nAChR) subunits and the α3β4 nAChR subtype in nicotine dependence and withdrawal. However, the involvement of these nAChR in relapse is not fully understood. We previously reported that the α3β4 nAChR partial agonist AT-1001 selectively decreases nicotine self-administration in rats without affecting food responding. In the present experiments, we examined the efficacy of AT-1001 in attenuating reinstatement of nicotine-seeking behavior in a model of stress-induced relapse. Rats extinguished from nicotine self-administration were treated with the pharmacological stressor yohimbine prior to AT-1001 treatment and reinstatement testing. We also examined whether AT-1001 produced any withdrawal-related effects when administered to nicotine-dependent rats. We found that AT-1001 dose-dependently reduced yohimbine stress-induced reinstatement of nicotine seeking. When administered to nicotine-dependent rats at the dose that significantly blocked nicotine reinstatement, AT-1001 elicited minimal somatic withdrawal signs in comparison to the nicotinic antagonist mecamylamine, which is known to produce robust withdrawal. Our data suggest that α3β4 nAChR-targeted compounds may be a promising approach for nicotine addiction treatment because they can not only block nicotine’s reinforcing effects, but also decrease motivation to relapse without producing significant withdrawal effects.

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“…These results suggest that α4β2* nAChRs mediate nicotine primed, but not cue-induced, reinstatement of drug seeking. This is further supported by a study showing that cue-induced reinstatement of nicotine seeking is attenuated following pretreatment with an α7*, but not α4β2*, nAChR antagonist [99]. Interestingly, chronic nicotine exposure promotes formation of α7* nAChR-NMDA receptor heterodimeric protein complexes in the hippocampus, and blocking this interaction attenuates cue-induced nicotine seeking [100].…”

Section: Neurotransmitter Mechanisms Regulating Nicotine Seekingmentioning

confidence: 81%

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

2018

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Tobacco-related morbidity and mortality continue to be a significant public health concern. Unfortunately, current FDA-approved smoking cessation pharmacotherapies have limited efficacy and are associated with high rates of relapse. Therefore, a better understanding of the neurobiological and neurophysiological mechanisms that promote smoking relapse is needed to develop novel smoking cessation medications. Here, we review preclinical studies focused on identifying the neurotransmitter and neuromodulator systems that mediate nicotine relapse, often modeled in laboratory animals using the reinstatement paradigm, as well as the plasticity-dependent neurophysiological mechanisms that facilitate nicotine reinstatement. Particular emphasis is placed on how these neuroadaptations relate to smoking relapse in humans. We also highlight a number of important gaps in our understanding of the neural mechanisms underlying nicotine reinstatement and critical future directions, which may lead toward the development of novel, target pharmacotherapies for smoking cessation.

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Effects of blockade of α4β2 and α7 nicotinic acetylcholine receptors on cue-induced reinstatement of nicotine-seeking behaviour in rats

Cited by 27 publications

References 106 publications

Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats

Effects of menthol and its interaction with nicotine-conditioned cue on nicotine-seeking behavior in rats

The α3β4 nAChR partial agonist AT-1001 attenuates stress-induced reinstatement of nicotine seeking in a rat model of relapse and induces minimal withdrawal in dependent rats

Neurobiological and Neurophysiological Mechanisms Underlying Nicotine Seeking and Smoking Relapse

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