The Neurobiology and Genetics of Nicotine and Tobacco

233 Pages·2015·4.178 MB·English

by  David J.K. Balfour, Marcus R. Munafò (eds.)

Current Topics in Behavioral Neurosciences 23
David J.K. Balfour
Marcus R. Munafò E ditors
The Neurobiology
and Genetics
of Nicotine and
Tobacco
Current Topics in Behavioral Neurosciences
Volume 23
Series editors
Mark A. Geyer, La Jolla, CA, USA
Bart A. Ellenbroek, Wellington, New Zealand
Charles A. Marsden, Nottingham, UK
Thomas R.E. Barnes, London, UK
About this Series
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ò
David J.K. Balfour Marcus R. Munaf
(cid:129)
Editors
The Neurobiology
and Genetics of Nicotine
and Tobacco
123
Editors
David J.K.Balfour Marcus R. Munafò
Ninewells Hospital School ofExperimental Psychology
Universityof DundeeMedical School Universityof Bristol
Dundee Bristol
UK UK
ISSN 1866-3370 ISSN 1866-3389 (electronic)
Current TopicsinBehavioral Neurosciences
ISBN 978-3-319-13664-6 ISBN 978-3-319-13665-3 (eBook)
DOI 10.1007/978-3-319-13665-3
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Preface
Whenoneofus(DJKB) first started studyingthepsychopharmacology ofnicotine
some40yearsagothenumbersofresearchersinterestedinthetopicwassmalland
could probably be accommodated around a large dinner table. Our understanding
of the potential hazards of smoking was at a fairly early stage as was our
understanding of the neural mechanisms that mediated the behavioral responses to
nicotine. At that time smoking was considered to be a habit, not an addiction, and
wasstillwidelyaccepted.Readerswhoarenotoldenoughtorememberthosetimes
may be familiar with the television series, Mad Men. That series gives you an
impression of how acceptable smoking was. Even into the 1980s, the fact that
neurones within the brain expressed nicotinic receptors was still debated among
some researchers. We have come a long way since that time, and now it is not
unusual to have 1,000 delegates or more at conferences on nicotine and tobacco,
and sessions dedicated to nicotine are not uncommon at many neuroscience con-
ferences. Moreover, public health policy is now driven by a sound evidence base
relating both to the toxicity of primary and second-hand (also known as environ-
mental) tobacco smoke and the plethora of neuroscience studies that have estab-
lished nicotine as one of the most widely studied recreational drugs. The primary
purpose of the chapters in this book and its companion volume is to explore the
extenttowhichthewiderangeofapproachesadoptedtoinvestigatethebehavioral
responses to nicotine and the molecular and neural mechanisms that mediate these
effects have opened our eyes to the properties of this unique and fascinating drug.
The chapters in the book are divided into two sections. The first considers the
molecular and genetic factors which influence the responses to nicotine and
tobacco. This section of the volume addresses the nature of the receptors in the
brain that mediate the responses to nicotine and how an understanding of the
genetic variation within these receptors, the neurotransmitter systems that respond
to them and the metabolic clearance of the drug impacts on nicotine and tobacco
dependence and its successful treatment. The second section focuses on the
evidence that nicotine may exert potentially beneficial effects within the brain,
particularly with regard to memory and attention. These cognitive effects
of the drug may explain, in part at least, why some people with underlying
v
vi Preface
psychopathologies of cognition, such as schizophrenia or attention deficit hyper-
activity disorder (ADHD), are particularly vulnerable to tobacco dependence and
resistanttotreatment.Thechaptersinthissectionofthebookalsoseektorelateour
understanding of the structure of neuronal nicotinic receptors to their effects on
attention and learning and memory. The last chapter of this section considers the
way in which learning theory can be recruited to explain some of the important
elements of nicotine dependence.
We hope that the volumes The Neurobiology and Genetics of Nicotine and
TobaccoandTheNeuropharmacologyofNicotineDependencewillprovidereaders
withacontemporaryoverviewofcurrentresearchonnicotinepsychopharmacology
and its role in tobacco dependence from leaders in this field of research and that
they will prove valuable to those who are developing their own research programs
in this important topic.
Dundee, Scotland David J.K. Balfour
Bristol Marcus R. Munafò
Contents
Structure of Neuronal Nicotinic Receptors . . . . . . . . . . . . . . . . . . . . . 1
Francesca Fasoli and Cecilia Gotti
Genetics of Smoking Behaviour . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Jennifer J. Ware and Marcus R. Munafò
Pharmacogenetics of Nicotine and Associated Smoking Behaviors . . . . 37
Julie-Anne Tanner, Meghan J. Chenoweth and Rachel F. Tyndale
Heterogeneity Across Brain Regions and Neurotransmitter
Interactions with Nicotinic Effects on Memory Function . . . . . . . . . . . 87
Edward D. Levin, Brandon J. Hall and Amir H. Rezvani
Nicotinic Receptors and Attention . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Britta Hahn
Nicotinic Receptors, Memory, and Hippocampus . . . . . . . . . . . . . . . . 137
Munir Gunes Kutlu and Thomas J. Gould
A Hierarchical Instrumental Decision Theory of Nicotine
Dependence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
Lee Hogarth and Joseph R. Troisi II
Smoking Abstinence and Neurocognition: Implications
for Cessation and Relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
F. Joseph McClernon, Merideth A. Addicott and Maggie M. Sweitzer
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
vii
Structure of Neuronal Nicotinic Receptors
Francesca Fasoli and Cecilia Gotti
Abstract Nicotinic acetylcholine receptors (nAChRs) are a critical component of
the brain’s cholinergic neurotransmission system that modulates important physi-
ological processes and whose dysfunction has been observed in patients with
neurodegenerativediseasesandmentalillness.nAChRsareaheterogeneousfamily
ofreceptorsubtypesconsistingofpentamericcombinationsofαandβsubunits,and
arewidelyexpressedthroughoutthecentralandperipheralnervoussystem.nAChR
subtypesshareacommonbasicstructurebuttheirbiophysicalandpharmacological
properties depend on their subunit composition, which is therefore central to
understanding receptor function in the nervous system and discovering new sub-
type-selective drugs. We briefly review some recent findings concerning the
structure and function of nAChRs, particularly the native subtypes.
(cid:1) (cid:1)
Keywords Neuronal nicotinic receptor subtypes Subunit composition
(cid:1) (cid:1) (cid:1)
Stoichiometry Nicotine αBungarotoxin Acetylcholine binding sites
Contents
1 Introduction.......................................................................................................................... 2
2 OverallStructureofNicotinicSubtypes............................................................................. 2
2.1 OrthostericAChBindingSites................................................................................... 5
2.2 AccessorySubunits..................................................................................................... 8
2.3 SubunitStoichiometry................................................................................................. 9
3 NativeSubtypes................................................................................................................... 9
3.1 TechniquesforStudyingNativenAChRs.................................................................. 9
3.2 AutoradiographicStudies............................................................................................ 10
3.3 BiochemicalandPharmacologicalStudiesofNativeSubtypes................................ 11
4 Conclusions.......................................................................................................................... 14
References.................................................................................................................................. 14
F.Fasoli(cid:1)C.Gotti(&)
DepartmentofMedicalBiotechnologiesandTranslationalMedicine,ConsiglioNazionale
DelleRicerche,InstituteofNeuroscience,UniversityofMilan,ViaVanvitelli32,
20129Milan,Italy
e-mail:[email protected]
©SpringerInternationalPublishingSwitzerland2015 1
D.J.K.BalfourandM.R.Munafò(eds.),TheNeurobiologyandGeneticsofNicotine
andTobacco,CurrentTopicsinBehavioralNeurosciences23,
DOI10.1007/978-3-319-13665-3_1
2 F.FasoliandC.Gotti
1 Introduction
The cholinergic system is one of the most important and phylogenetically oldest
nervouspathways.Acetylcholine(ACh)istheneurotransmitterthatissynthesized,
stored, and released by cholinergic neurons, and the key molecules that transduce
the ACh message are the muscarinic metabotropic receptors and the ionotropic
neuronal nicotinic acetylcholine receptors (nAChRs) (Picciotto et al. 2012).
nAChRs are a heterogeneous family of ion channels ubiquitously expressed in the
central nervous system (CNS) that by responding to the endogenous neurotrans-
mitter acetylcholine (ACh) and nicotine, the most widespread drug of abuse, are
implicated in a variety of physiological processes (reviewed in Hurst et al. 2013).
nAChRsactivationexcitestargetcellsandmediatesfastsynaptictransmissionin
autonomous ganglionic neurons and in some brain areas, but anatomical and
functional evidence suggests that the nAChRs in brain are preferentially located at
preterminalandpresynapticsiteswheretheyregulatethereleaseofbothexcitatory
andinhibitoryneurotransmitters(reviewedinAlbuquerqueetal.2009;Jensenetal.
2005).
nAChRs and nicotinic mechanisms contribute to cognitive function and their
declineordysfunctionhasbeenobservedinneurodegenerativediseasesandmental
illness. In addition genetic studies have linked nAChRs to epilepsy and schizo-
phrenia,andstudiesofmutant(knockoutorknockin)micehaveshownthattheyare
involved in pain mechanisms, anxiety, and depression (reviewed in Changeux
2010; Drenan and Lester 2012; Gotti and Clementi 2004; Hurst et al. 2013;
Picciotto et al. 2001). nAChRs are particularly important in two critical periods of
brain life: early pre- and post-natal circuit formation, and age-related cell degen-
eration.Theyareinvolvedinneuronalsurvival,asithasbeenshownthatnicotinic
agonistsare neuroprotective in both invivoand in vitro models. Furthermore, it is
becoming evident that the perturbation of cholinergic nicotinic neurotransmission
can lead to various diseases during development, adulthood, and aging (Picciotto
and Zoli 2008). As a number of comprehensive reviews (Albuquerque et al. 2009;
Changeux 2009; Gotti et al. 2009) have described the structure and function of
nAChRs, the aim of this paper is to provide a brief overview of the most recent
findings on the structure of the brain nAChR subtypes.
2 Overall Structure of Nicotinic Subtypes
nAChRs were initially identified by means of ligand binding assays using radio-
activeligands,whichshowedthat125I-αBungarotoxin(αBgtx)and3H-nicotinebind
to receptors with different anatomical and pharmacological distributions (Clarke
et al. 1985).
ThepharmacologicalheterogeneityofnAChRsrevealedbythese ligandstudies
waslaterconfirmedandextendedbymeansofthemolecularcloningofafamilyof