Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

Varani, Andrés Pablo; Moutinho, Lirane Machado; Bettler, Bernhard; Balerio, Graciela N.

doi:10.1016/j.neuropharm.2012.06.006

Cited by 34 publications

(36 citation statements)

References 61 publications

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“…One could then speculate that imbalances between excitatory and inhibitory circuits could also contribute to alteration in nocifensive behaviors displayed by BTBR and Fmr1 -KO mice. Further, as researchers have shown that the antinociceptive effects of nicotine are altered in the setting of decreased GABAergic signaling (Varani et al, 2012), it is also conceivable that imbalances in excitatory/inhibitory signaling in BTBR, could at least in part have contributed to the differential effects of nicotine comparing BTBR and control mice. In turn, these findings in BTBR mice are compatible with the hypothesis that, chronic nicotine, possibly by its interaction with the GABAergic system, modulates nocifensive response as well as social deficits and repetitive behavior.…”

Section: Discussionmentioning

confidence: 99%

Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system

et al. 2016

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Caretakers and clinicians alike have long recognized that individuals with autism spectrum disorder (ASD) can have altered sensory processing, which can contribute to its core symptoms. However, the pathobiology of sensory alterations in ASD is poorly understood. Here we examined nocifensive behavior in ASD mouse models, the BTBR T+Itpr3tf/J (BTBR) and the fragile-X mental retardation-1 knockout (Fmr1-KO) mice. We also examined the effects of nicotine on nocifensive behavior given that nicotine, a nicotinic cholinergic receptor (nAChR) agonist that has antinociceptive effects and was shown to improve social deficits and decrease repetitive behaviors in BTBR mice. Compared to respective controls, both BTBR and Fmr1-KO had hyporesponsiveness to noxious thermal stimuli and electrical stimulation of C-sensory fibers, normal responsiveness to electrical stimulation of Aβ- and Aδ-fiber, and hyperresponsiveness to visceral pain after acetic acid intraperitoneal injection. In BTBR, nicotine at lower doses increased, whereas at higher doses, it decreased hotplate latency compared to vehicle. In a significantly different effect pattern, in control mice, nicotine had antinociceptive effects to noxious heat only at the high dose. Interestingly, these nocifensive behavior alterations and differential responses to nicotine antinociceptive effects in BTBR mice were associated with significant downregulation of α3, α4, α5, α7, β2, β3, and β4 nAChR subunits in several cerebral regions both, during embryonic development and adulthood. Taken together, these findings further implicate nAChRs in behaviors alterations in the BTBR model and lend support to the hypothesis that nAChRs may be a target for treatment of behavior deficits and sensory dysfunction in ASD.

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Section: Discussionmentioning

confidence: 99%

Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system

et al. 2016

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“…In a recent study, it was shown that nicotine withdrawal led to a decrease in the number of Fos positive cells in the BNST, BLA, and dentate gyrus. Nicotine withdrawal did not affect Fos expression in a wide range of other brain sites including the NAcc, cingulate cortex, caudate putamen, CA1 and CA3 region of the hippocampus, and medial habenular nucleus (Varani et al 2012). …”

Section: Neuronal Activation Of Peptide Systemsmentioning

confidence: 94%

“…One of the first studies that investigated Fos expression in rats undergoing withdrawal showed that withdrawal leads to an increase in Fos expression in the CeA but not in other brain sites (Panagis et al 2000). Although pharmacological studies suggest that withdrawal leads to the activation of brain stress systems, several Fos studies suggest that nicotine withdrawal leads to decreased activity in brain sites (Balerio et al 2004; Varani et al 2012). In a recent study, it was shown that nicotine withdrawal led to a decrease in the number of Fos positive cells in the BNST, BLA, and dentate gyrus.…”

Section: Neuronal Activation Of Peptide Systemsmentioning

confidence: 99%

Neuropeptide systems and new treatments for nicotine addiction

Bruijnzeel

2016

Psychopharmacology

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RATIONALE The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking. RESULTS The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking. CONCLUSION Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience.

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“…Mecamylamine-precipitated somatic nicotine withdrawal signs were attenuated in GABA B −/− mice (Varani et al 2012). Additionally, the reduction in c-Fos positive nuclei in the bed nucleus of the stria terminalis, basolateral amygdaloid nucleus, and the hippocampal dentate gyrus observed in GABA B +/+ mice after precipitated nicotine withdrawal, was absent in GABA B −/− mice, an effect that may be related to the attenuated somatic signs (Varani et al 2012).…”

Section: Recent Advances In Mechanisms Of Nicotine Withdrawal: Finmentioning

confidence: 99%

New mechanisms and perspectives in nicotine withdrawal

et al. 2015

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Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available.

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Acute behavioural responses to nicotine and nicotine withdrawal syndrome are modified in GABAB1 knockout mice

Cited by 34 publications

References 61 publications

Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system

Altered nocifensive behavior in animal models of autism spectrum disorder: The role of the nicotinic cholinergic system

Neuropeptide systems and new treatments for nicotine addiction

New mechanisms and perspectives in nicotine withdrawal

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