Involvement of α6 nicotinic receptor subunit in nicotine-elicited locomotion, demonstrated by in vivo antisense oligonucleotide infusion

N, le Novère; Zoli, Michèle; Léna, Clément; Ferrari, R; Picciotto, Marina R.; Merlo‐Pich, Emilio; Jp, Changeux

doi:10.1097/00001756-199908200-00012

Cited by 78 publications

(39 citation statements)

References 9 publications

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“…However, previous in vivo evidence for a physiological or pharmacological role of these receptors was in part contradictory. In accordance with present findings, intra-VTA infusion of anti-␣6 oligonucleotides partially inhibits nicotine-elicited habituated locomotion in rats (Le Novère et al, 1999), and mice expressing gain-of-function ␣6* nAChRs show spontaneous hyperlocomotion that is exaggerated by low dose of systemic nicotine (Drenan et al, 2008). Instead, no significant change in systemic nicotine-elicited DA release in nAc was detected in ␣6 Ϫ/Ϫ mice .…”

Section: Discussionsupporting

confidence: 91%

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Gotti¹,

Guiducci²,

Tedesco³

et al. 2010

J. Neurosci.

210

236

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␣6* nicotinic acetylcholine receptors (nAChRs) are highly and selectively expressed by mesostriatal dopamine (DA) neurons. These neurons are thought to mediate several behavioral effects of nicotine, including locomotion, habit learning, and reinforcement. Yet the functional role of ␣6* nAChRs in midbrain DA neurons is mostly unknown. The aim of this study was to determine the composition and in vivo functional role of ␣6* nAChR in mesolimbic DA neurons of male rats. Immunoprecipitation and immunopurification techniques coupled with cell-specific lesions showed that the composition of ␣6* nAChR in the mesostriatal system is heterogeneous, with (non-␣4)␣6␤2* being predominant in the mesolimbic pathway and ␣4␣6␤2* in the nigrostriatal pathway. We verified whether ␣6* receptors mediate the systemic effects of nicotine on the mesolimbic DA pathway by perfusing the selective antagonists ␣-conotoxin MII (CntxMII) (␣3/␣6␤2* selective) or ␣-conotoxin PIA (CntxPIA) (␣6␤2* selective) into ventral tegmental area (VTA). The intra-VTA perfusion of CntxMII or CntxPIA markedly decreased systemic nicotine-elicited DA release in the nucleus accumbens and habituated locomotion; the intra-VTA perfusion of CntxMII also decreased the rate of nicotine infusion in the maintenance phase of nicotine, but not of food, self-administration. Overall, the results of these experiments show that the ␣6␤2* nAChRs expressed in the VTA are necessary for the effects of systemic nicotine on DA neuron activity and DA-dependent behaviors such as locomotion and reinforcement, and suggest that ␣6␤2*-selective compounds capable of crossing the blood-brain barrier may affect the addictive properties of nicotine and therefore be useful in the treatment of tobacco dependence.

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Section: Discussionsupporting

confidence: 91%

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Gotti¹,

Guiducci²,

Tedesco³

et al. 2010

J. Neurosci.

210

236

View full text Add to dashboard Cite

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“…Thus, nicotinic receptor drugs may be beneficial in restoring activity closer to normal levels. Indeed, administration of nicotine or nicotinic agonists seems to ameliorate motor deficits after nigrostriatal degeneration in both rodents and monkeys (Janson et al, 1988;Schneider et al, 1998;Domino et al, 1999;le Novere et al, 1999). In humans, cigarette smoking, the nicotine patch, or nicotine gum also alleviate some of the motor dysfunction observed with Parkinson's disease (see .…”

mentioning

confidence: 99%

Differential Declines in Striatal Nicotinic Receptor Subtype Function after Nigrostriatal Damage in Mice

et al. 2003

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Nigrostriatal damage leads to a reduction in striatal nicotinic acetylcholine receptors (nAChRs) in rodents, monkeys, and patients with Parkinson's disease. The present studies were undertaken to investigate whether these nAChR declines are associated with alterations in striatal nAChR function and, if so, to identify the receptor subtypes involved. To induce nigrostriatal damage, mice were injected with the selective dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP

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“…The use of viral vectors to express nAChR subunits in specific cells/brain loci on the background of a constitutive knockout has been extremely powerful in identifying the anatomical basis for behavioral and neurochemical effects of nicotine [54,96]. Similarly, antisense oligonucleotides have been used to decrease the expression of specific nAChRs subunits in adulthood [97], although this approach has only been used for the α6 subunit.…”

Section: Inbred/selected Strainsmentioning

confidence: 99%

Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction

Mineur

Picciotto

2008

Biochemical Pharmacology

122

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Human twin studies have suggested that there is a substantial genetic component underlying nicotine dependence, ongoing smoking and ability to quit. Similarly, animal studies have identified a number of genes and gene products that are critical for behaviors related to nicotine addiction. Classical genetic approaches, gene association studies and genetic engineering techniques have been used to identify the gene products involved in nicotine dependence. One class of genes involved in nicotinerelated behavior is the family of nicotinic acetylcholine receptors (nAChRs). These receptors are the primary targets for nicotine in the brain. Genetic engineering studies in mice have identified a number of subunits that are critical for the ability of nicotine to activate the reward system in the brain, consisting of the dopaminergic cell bodies in the ventral tegmental area and their terminals in the nucleus accumbens and other portions of the mesolimbic system. In this review we will discuss the various lines of evidence suggesting that nAChRs may be involved in smoking behavior, and will review the human and animal studies that have been performed to date examining the genetic basis for nicotine dependence and smoking.

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Involvement of α6 nicotinic receptor subunit in nicotine-elicited locomotion, demonstrated by in vivo antisense oligonucleotide infusion

Cited by 78 publications

References 9 publications

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Nicotinic Acetylcholine Receptors in the Mesolimbic Pathway: Primary Role of Ventral Tegmental Area α6β2* Receptors in Mediating Systemic Nicotine Effects on Dopamine Release, Locomotion, and Reinforcement

Differential Declines in Striatal Nicotinic Receptor Subtype Function after Nigrostriatal Damage in Mice

Genetics of nicotinic acetylcholine receptors: Relevance to nicotine addiction

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