Tolerance to nicotine in mice lacking α7 nicotinic receptors

Naylor, Christopher G.; Quarta, Davide; Fernandes, Cathy; Stolerman, I. P.

doi:10.1007/s00213-005-2187-5

Cited by 21 publications

(19 citation statements)

References 26 publications

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“…In addition, Jackson and colleagues [77] have found no difference between α7 KO and WT mice in avoidance learning as measured by nicotine CPA. Finally, the locomotor suppressant effect of acute nicotine and tolerance to the effects of nicotine on locomotion are equivalent between α7 KO and WT mice [122]. Although these data suggest that α7 nAChRs are not critically involved in many of the effects of nicotine, these results do not rule out the possibility that α7 nAChRs play an ancillary role in these phenotypes.…”

Section: The α7 Nachr Subunitmentioning

confidence: 73%

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Portugal

Gould

2008

Behavioural Brain Research

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Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins.

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Section: The α7 Nachr Subunitmentioning

confidence: 73%

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Portugal

Gould

2008

Behavioural Brain Research

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“…152,153 The development of nicotine tolerance did not differ between a7-KO and WT mice. 154 Somatic withdrawal signs (after intraperitoneal injection of nAChR antagonist to induce nicotinic withdrawal) are reduced in chrna7 KO mice relative to WT littermates. 155 However, other reports suggest that a7-subunit involvement in withdrawal is restricted to somatic signs and does not affect other withdrawal symptoms such as affective ones, 77,143 whereas others do not support the role of this subunit in somatic withdrawal signs either.…”

Section: Chrna7mentioning

confidence: 99%

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

Greenbaum¹,

Lerer²

2009

Mol Psychiatry

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Nicotine dependence (ND), a major public health challenge, is a complex, multifactorial behavior, in which both genetic and environmental factors have a role. Brain nicotinic acetylcholine receptor (nAChR)-encoding genes are among the most prominent candidate genes studied in the context of ND, because of their biological relevance as binding sites for nicotine. Until recently, most research on the role of nAChRs in ND has focused on two of these genes (encoding the a4-and b2-subunits) and not much attention has been paid to the possible contribution of the other nine brain nAChR subunit genes (a2-a3, a5-a7, a9-a10, b3-b4) to the pathophysiology and genetics of ND. This situation has changed dramatically in the last 2 years during which intensive research had addressed the issue, mainly from the genetics perspective, and has shown the importance of the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 loci in ND-related phenotypes. In this review, we highlight recent findings regarding the contribution of non-a4/b2-subunit containing nAChRs to ND, based on several lines of evidence: (1) human genetics studies (including linkage analysis, candidate-gene association studies and whole-genome association studies) of several ND-related phenotypes; (2) differential pharmacological and biochemical properties of receptors containing these subunits; (3) evidence from genetically manipulated mice; and (4) the contribution of nAChR genes to ND-related personality traits and neurocognitive profiles. Combining neurobiological genetic and behavioral perspectives, we suggest that genetic susceptibility to ND is not linked to one or two specific nAChR subtype genes but to several. In particular, the a3, a5-6 and b3-4 nAChR subunit-encoding genes may play a much more pivotal role in the neurobiology and genetics of ND than was appreciated earlier. At the functional level, variants in these subunit genes (most likely regulatory) may have independent as well as interactive contributions to the ND phenotype spectrum. We address methodological challenges in the field, highlight open questions and suggest possible pathways for future research.

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“…Mice lacking ␣7 nAChR subunits have subtle phenotypes, such as decrements in sustained attention (Young et al, 2004) and impairments in passive avoidance learning (Marubio and Paylor, 2004). Although ␣7 KO mice show alterations in DA neuron firing rates in response to endogenous ACh , they are largely normal with respect to nicotine and the DA reinforcement pathway (Naylor et al, 2005;Walters et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations

Drenan

Lester

2012

Pharmacol Rev

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Tolerance to nicotine in mice lacking α7 nicotinic receptors

Cited by 21 publications

References 26 publications

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

Differential contribution of genetic variation in multiple brain nicotinic cholinergic receptors to nicotine dependence: recent progress and emerging open questions

Insights into the Neurobiology of the Nicotinic Cholinergic System and Nicotine Addiction from Mice Expressing Nicotinic Receptors Harboring Gain-of-Function Mutations

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