Neuroscience of Nicotine: Mechanisms and Treatment

Cover
NEUROSCIENCE
OF NICOTINE:

MECHANISMS AND TREATMENT
Copyright
Contributors
Preface
Editorial Advisors
1
Understanding Tobacco Use in Different Countries
	Introduction
	Basic Concepts of Tobacco Epidemiology
	The Demand for Tobacco Products: A Brief Introduction
		Price Elasticity and Changes in Quantity Demanded
		Changes in Demand and Income Elasticity
		Using the Demand Model to Understand Smoking Prevalence
	An Overview of Tobacco Use in Different Countries
	Mini-Dictionary of Terms
	Key Facts on Tobacco Use
	Summary Points
	References
2
Maternal Smoking and Fetal Brain Outcome: Mechanisms and Possible Solutions
	Introduction
	Maternal Smoking and Brain Development
	Maternal Smoking and Neurocognitive Outcome
	Maternal Smoking and HI Encephalopathy
	Potential Mechanisms
		Brain Inflammatory Response
		Brain Oxidative Stress
			ROS
			Antioxidant Defense System
		Mitochondrial Function and Integrity
			Mitochondrial Membrane Functional Units
			Mitochondrial Integrity
				Fission Machinery
				Fusion Machinery
	Gender Difference in the Response to Maternal Smoking
	l-Carnitine as a Therapeutic Strategy
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Maternal Smoking
	Summary Points
	References
3
Nicotine Effects in Adolescents
	Nicotine Reward in Adolescent and Adult Males and Females
	Nicotine During Adolescence Increases Effects of Subsequent Drug Administration
	Nicotine Effects on Neurochemistry in Adolescence
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of Adolescent Nicotine Effects
	Summary Points
	References
4
 The Impact of Traditional Cigarettes and E-Cigarettes on the Brain
	Introduction
	Structural Changes of Brain Among the Nicotine Users
	Functional Changes of the Brain Among Conventional Cigarettes Smokers
	Functional Changes of the Brain Among Electronic Cigarettes Users
	Nicotine Withdrawal Symptoms
	Nicotine and Reward Circuit
	Impact of Nicotine on Developing Brain
	The Nicotine-Induced Oxidative Stress and Neuronal Apoptosis
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of the Reward Circuit
	Summary Points
	References
5
Reduction of Nicotine in Tobacco and Impact
	Strategies to Prevent Addiction and Reduce Tobacco Use
	Public Perception of Low-Nicotine Cigarette Health Risks
	Is it Advantageous to Reduce Nicotine Content in Tobacco Products? Evidence From Epidemiological and Experimental St ...
	Is it Advantageous to Reduce Nicotine Content in Tobacco Products? Most Evidence From Animal Models of Exposure Indi ...
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of Nicotine Reduction in Tobacco Research
	Summary Points
	References
6
 Prenatal Nicotine Exposure and Neuronal Progenitor Cells
	Introduction
	Neuronal Progenitor Cells in Developing Brain
	Nicotinic Acetylcholine Receptors in NPCs
	Impact of Nicotine on Prenatal Neurogenesis
	The Relevant Functions of Involved nAChRs
	Future Directions
	Mini-Dictionary of Terms
	Key Facts About Prenatal Tobacco Exposure
	Summary Points
	References
7
Synaptically Located Nicotinic Acetylcholine Receptor Subunits in Neurons Involved in Dependency to Nicotine
	Introduction
	nAChRs Structure and Binding
	Location
		Presynaptic
		Postsynaptic
	The nAChR in Mesolimbic Circuitry
	Endogenous ACh and nAChRs
	Conclusions
	7.1IntroductionNicotine does not occur naturally in the mammalian body. However, recognition of the ability of nicotine to str
	7.1IntroductionNicotine does not occur naturally in the mammalian body. However, recognition of the ability of nicotine to str
	References
8
Cotinine as a Possible Allosteric Modulator of Nicotine Effects in Various Models
	Introduction
	Nicotinic Acetylcholine Receptors
	Cotinine
	Nicotine/Cotinine and Planarians
	The Principle of Microscopic Reversibility
	Acknowledgments
	Mini-Dictionary of Terms
	Key Facts
	Summary Points
	References
9
Nicotine, Neural Plasticity, and Nicotine's Therapeutic Potential
	Introduction
	Nicotine as a Neuroprotectant
	Nicotine and Neurotrophic Factors
	Nicotine, nAChRs, and Relationship to Neurotrophic Factors
	Nicotine, BDNF, and Addiction
	Functional Improvement in Animal Models: Parkinson's Disease
	Functional Improvement in Animal Models: Alzheimer's Disease
	Nicotine Neuroprotection Against Cognitive Impairments Due to Brain Insult
	Nicotine and Neuroinflammation
	Concluding Remarks
	Summary Points
	References
10
Habenular Synapses and Nicotine
	Introduction
	The Habenula: A Highly Conserved Circuit
	Nicotinic Acetylcholine Receptor Diversity in the MHb-IPN
	Electrophysiology of Habenular Neurons
	Mini-Dictionary of Terms
	Summary Points
	References
11
Nicotine Neuroprotection of Brain Neurons: The Other Side of Nicotine Addiction
	Introduction
	Epidemiological Studies of Neurodegenerative Diseases: Nicotine and Smoking
	Clinical Studies of Neurodegenerative Diseases: The Influence of Tobacco Vs Nicotine
	Cellular Effects of Nicotine on In Vitro Models
	Neuroprotective Effect of Nicotine on Mouse, Rat, or Monkey Models In Vivo
	Nicotine Affects Intracellular Signaling
	Mini-Dictionary of Terms
	Key Facts of Nicotine Neuroprotection
	Summary Points
	References
12
Linking Nicotine, Menthol, and Brain Changes
	Introduction
	Brief History of Menthol Cigarettes
	Menthol and Nicotine: Early Clinical Findings
	Menthol's Actions on Cys-Loop Receptors
	Menthol Enhances Nicotine Reward by Altering Midbrain Dopamine Neurons
		Menthol Enhances Nicotine-Induced Upregulation of nAChRs
		Menthol Enhances Nicotine-Induced Changes in Dopamine Neuron Excitability
	Menthol By Itself Alters nAChRs on Midbrain Dopamine Neurons
		Menthol Alone Upregulates nAChRs
		Menthol-Alone Abolishes Nicotine Reward-Related Behavior
	Summary
	Mini-Dictionary of Terms
	Key Facts of Menthol
	Summary Points
	References
13
Cigarette Smoking and Nicotine: Effects on Multiple Sclerosis
	Introduction
	Cigarette Smoking and MS risk
	Cigarette Smoking and MS Progression and Symptoms Worsening
	Mechanisms Linking Cigarette Smoking and Multiple Sclerosis
	Nicotine and Multiple Sclerosis
	Conclusion
	Mini-Dictionary of Terms
	Summary Points
	References
14
 Tobacco and Positron-Emission Tomography (PET) of the Dopaminergic System: A Review of Human Studies
	Tobacco Smoking and the Dopaminergic System
		Positron-Emission Tomography
		Dopamine
	PET Studies in Human Smokers
		[11C]-Raclopride
		[18F]-Fallypride
		[11C]-FLB-457
		[11C]-(+)-PHNO
		[11C]-SCH 23390
		[18F]-Fluorodopa
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Radiotracers in PET Scans
	Summary Points
	References
15
Resting-State Functional Connectivity Imaging and Nicotine Dependence
	Introduction
	Assessing Resting-State Functional Connectivity
		Regions of Interest and Resting-State Networks in fMRI Data
		Static rsFC Using Functional Magnetic Resonance Imaging
		Dynamic rsFC Using Functional Magnetic Resonance Imaging
	Resting-State Connectivity Dysfunctions
		Insula
		Anterior cingulate cortex
		The Default Mode Network
		Executive Control and Salience Networks
		DMN-SN-ECN-Network Model of Nicotine Addiction
	Treatment Implications of Resting-State Functional Connectivity
	Mini-Dictionary of Terms
	Key Facts of Resting-State Brain Networks
	Summary Points
	References
16
Functional Magnetic Resonance Imaging of Acute Nicotine Effects
	Introduction
	Task-Based fMRI Studies
	Resting-State fMRI Studies
	Outlook
	Mini-Dictionary of Terms
	Key Facts on Functional Magnetic Resonance Imaging
	Summary Points
	References
17
Nicotine Dependence in Schizophrenia: Contributions of Nicotinic Acetylcholine Receptors
	Introduction
	Pharmacology of nAChRs
	nAChR Expression in Schizophrenia
	nAChRs and the Positive Symptoms of Schizophrenia
	Nicotine and Cognition in Schizophrenia: Neuromodulation by nAChRs
	Contributions of nAChRs to the Negative Symptoms of Schizophrenia
	nAChRs Modulation as Possible Treatments of Schizophrenia
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of Schizophrenia
	Summary Points
	References
18
Attentional Bias and Smoking
	Introduction
	Paradigms and Measures
	Clinical Relevance
	Current Challenges
	Summary/Future Directions
	Mini-Dictionary of Terms
	Key Facts of Attentional Bias Assessment
	Summary Points
	References
19
Effects of Nicotine on Inhibitory Control in Humans
	Introduction
	Effects of Nicotine on Response Inhibition and Interference Control
		Antisaccade Tasks
		Stop-Signal Tasks
		Go/No-Go Tasks
		Stroop Tasks
		Flanker Tasks
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of Inhibitory Control
	Summary Points
	References
20
Nicotine, Corticotropin-Releasing Factor, and Anxiety-Like Behavior
	Introduction
	Corticotropin-Releasing Factor (CRF)-Like Peptides
	Corticotropin-Releasing Factor Receptors
	Animal Models to Study Nicotine-Withdrawal-Induced Anxiety-Like Behavior
	Corticotropin-Releasing Factor, Nicotine Withdrawal, and Anxiety
	Role of CRF2 Receptors in Nicotine Withdrawal
	CRF and Anhedonia Associated With Nicotine Withdrawal
	Concluding Remarks
	Mini-Dictionary of Terms
	Key Facts of Tobacco Smoking
	Summary Points
	Acknowledgments
	References
21
6-Hydroxy-l-Nicotine and Memory Impairment
	Introduction
	Implication to Treatments
	Nicotine Derivatives in Bacteria
	Nicotine Catabolism in Arthrobacter nicotinovorans
	6HLN Is Able to Interact With nAChRs
	6HLN Produced Using an Arthrobacter-Based Biotechnology
	Mini-Dictionary of Terms
	Key Facts of Memory impairment
	Summary Points
	Acknowledgment
	References
22
Cotinine and Memory: Remembering to Forget
	Introduction
	Cotinine Ameliorates Memory in AD Mice
	Cotinine Prevents Memory Loss in Mouse Models of Posttraumatic Stress Disorder
	Cotinine Restore Astrocytes Number and Function Affected by Chronic Stress
	Signaling Pathways Activated by Cotinine in Rodent Models of Depression and PTSD
		Cotinine Has Antiinflammatory Effects by Modulating the nAChRs
		Cotinine Stimulates Akt and ERK Signaling
	Cotinine Restore Working Memory Abilities After Chemotherapy in Female Rats
	Cotinine Restores Memory in Animal Models of Autism Spectrum Disorder and Schizophrenia
	Key Facts
	Summary Points
	Mini-Dictionary of Terms
	References
23
Nicotine in Aberrant Learning and Corticostriatal Plasticity
	Introduction
	Parkinson's Disease, Nicotine, and Neuroprotection
	The Aberrant Motor Learning Hypothesis
	Nicotine Mitigates Aberrant Motor Learning Induced by Dopamine Deficiency
	Nicotine Addiction and Aberrant Learning
	Nicotine-Induced Silent Synapses and Altered Corticostriatal Plasticity
	The Chronic Nicotine Puzzle
	Chronic Nicotine and Synaptic Stability: An Initial Hypothesis
	Mini-Dictionary of Terms
	Key Facts of Silent Synapses
	Summary Points
	References
24
Prenatal Nicotine Exposure and Impact on the Behaviors of Offspring
	Introduction
	Prenatal Nicotine Exposure
	Impact on Behaviors of Offspring
	Emotional Behavior
	Cognitive Behavior
	Addictive Behavior
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Nicotine Replacement Therapy during Pregnancy
	Summary Points
	References
25
Craving in Substance Use Disorders With a Focus on Cigarette Smoking
	Introduction
	The Construct of Craving
	Craving, Cognition, and Self-Regulation
	Integrating Neurobiological and Behavioral Investigations of Craving
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of Functional Brain Imaging
	Summary Points
	References
26
The Acute Effect of Exercise on Cravings and Withdrawal Symptoms
	Cravings
		Effect of Acute Exercise on Cravings
		Clinical Importance
	Tobacco Withdrawal Symptoms
		Effect of Acute Exercise on TWS
		Clinical Importance
	Mechanisms
	Summary of the Clinical Importance of Acute Exercise
	Mini-Dictionary of Terms
	Key Facts of Physical Activity and Exercise
	Summary Points
	References
27
CRF2 Receptor Agonists and Nicotine Withdrawal
	Mini-Dictionary of Terms
	Key Facts of the Elevated Plus-Maze Test
	Key Facts of the Forced Swim Test
	Key Facts of the Chemofluorescent Assay
	Summary Points
	References
28
Delirium and Nicotine Withdrawal
	Introduction
	Nicotine Use as a Risk Factor for Delirium: A Theoretical Conceptualization
		Clinical Features of Delirium and Nicotine Withdrawal
	Neurobiological Links Between Nicotine Withdrawal and Delirium
		Dysregulation of the Cholinergic System
		Dysregulation of Other Neurotransmitters
		Decreased Serotonergic Function in Midbrain
		Hypothalamic-Pituitary Axis (HPA) and Corticotrophin Releasing Factor Dysregulation
		Neuronal Inflammation and Increased Susceptibility to Delirium
	Clinical Evidence
	Nicotine Replacement Therapy in Delirium
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Nicotine Withdrawal Delirium
	Summary Points
	References
29
Postoperative Nicotine Withdrawal
	Introduction
	Postoperative Delirium
	Pathogenesis
	Causes of Postoperative Delirium
	Clinical Presentation
	Diagnosis
	Nicotine Withdrawal in Postoperative Patients
	Diagnosis of Nicotine Withdrawal
	Treatment
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Postoperative Delirium
	Summary Points
	References
30
Nicotine and Alpha3beta2 Neuronal Nicotinic Acetylcholine Receptors
	Introduction
	Nicotine Sensitivity by Subtype
	Nicotine-Induced Upregulation
	Location
	Physiological Effect of Nicotine
	Variants of the α3 Subunit
	Implications for Treatment
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Neuronal Nicotinic Acetylcholine Receptors
	Summary Points
	References
31
Nicotine Addiction and Alpha4beta2* Nicotinic Acetylcholine Receptors
	Introduction
	α4β2* nAChRs in Nicotine Self-Administration and Reinstatement
	β2-Containing nAChRs in Nicotine Self-Administration
	α4-Containing nAChRs in Nicotine Self-Administration
	α4β2* nAChR Partial Agonists in Nicotine Self-Administration and Reinstatement
	Positive Allosteric Modulators of α4β2* nAChRs in Nicotine Addiction and Reinstatement
	Implications for Treatment and Conclusions
	Mini-Dictionary of Terms
	Key Facts of Nicotine Self-Administration
	Summary Points
	References
32
The Medial Habenula-Interpeduncular Nucleus Pathway in Nicotine Sensitization: The Role of α3β4 Nicotinic Ace ...
	Introduction
	Expression of the α3β4 nAChR
	The α3β4 nAChR in Nicotine Addiction
	Nicotine Sensitization: An Important Model in Addiction Research
	Animal Models of Nicotine Sensitization
	The α3β4 nAChR in Nicotine Sensitization
	Downstream Targets of the MHb
	Substance P as a Co-neurotransmitter
	The NK1R in Addiction and Nicotine Sensitization
	The NK1 Receptor in Nicotine Sensitization
	Putative Neurocircuitry Regulating the MHb-IPN Effects on Nicotine Sensitization
	Mini-Dictionary of Terms
	Key Facts of the Habenula-Interpeduncular Nucleus Pathway
	Summary Points
	References
33
 Targeting Nicotinic Acetylcholine Receptors for the Treatment of Pain
	Introduction to Nicotinic Acetylcholine Receptors
	The α4β2* nAChRs in Pain Modulation
	The α7 nAChRs in Pain Modulation
	The α9/α9α10 nAChRs in Pain Modulation
	Conclusions
	Mini-Dictionary of Terms
	Key Facts of nAChRs and Their Ligands
	Summary Points
	Acknowledgments
	References
34
Pharmacology of Muscle-Type Nicotinic Receptors
	Introduction
	Overall Structure and Function of nAChRm
	Mechanisms of nAChRm Modulation
	Different Therapeutic Drugs Modulate nAChRm Function
	Future Perspectives
	Mini-Dictionary of Terms
	Key Facts of Desensitization
	Key Facts of nAChRm Disorders
	Summary Points
	Acknowledgment
	References
35
Involvement of Opioid Receptors in Nicotine-Related Reinforcement and Pleasure
	Introduction
	The Heart of the Matter: Nicotine Interoception
	Preclinical Evidence: Nicotine Interoception
	Nicotine as a Reinforcer
	Nicotine-Induced Reward Sensitivity
	Into the Clinic: Opioid Antagonists and Tobacco Dependence
	Mini-Dictionary of Terms
	Key Facts of ORs
	Summary Points
	References
36
Nicotine-Induced Kindling: Influences of Age, Sex, and Prevention by Antioxidants
	Introduction
	Kindling Phenomenon and Its Relation to Epileptogenesis and to Neuropsychiatric Disorders
	Nicotine-Induced Kindling
		Sex and Age Influences
		Prevention by the Use of Antioxidants
	Conclusion and Future Perspectives
	Mini-Dictionary of Terms
	Key Facts of Kindling Model
	Key Facts of Nicotine-Induced Kindling
	Summary Points
	References
37
Nicotine Reward and Abstinence: Role of the CB1 Receptors
	INTRODUCTION
		Nicotine Addiction
		How to Probe Nicotine Addictive Behaviors?
	The CB1 Receptor Direct Pharmacotherapy
	The CB1 Receptor Indirect Pharmacotherapy
	Acute vs Chronic Treatment With the CB1-Targeting Pharmacotherapy
	Mini-Dictionary of Terms
	Key Facts of Depressive-Like Behaviors
	Summary Points
	References
38
The Therapeutic Potential of the Cognitive-Enhancing Effects of Nicotine and Other Nicotinic Acetylcholine Re ...
	Which nAChR Subtypes to Target?
	Overdosed?
	No Such Thing as a Free Lunch?
	A Naive Premise?
	Conclusions
	Mini-Dictionary of Terms
	Key Facts on Nicotinic Agonist Therapy for Cognitive Deficits
	Summary Points
	References
39
Nicotine and Dopamine DA1 Receptor Pharmacology
	Introduction
		Dopamine DA1 Receptors, Localization and Signaling
		Nicotine and DA1 Receptors-Molecular Insight
			PKA/DARPP-32/PP1 Signaling Cascade
			Genetic Background
	DA1 Receptors and Behavioral Effects of Nicotine
		Motivational Effects
		Other Nicotine-DA1 Receptors Associations
	Mini-Dictionary of Terms
	Key Facts of Link Between Nicotine and D1 Receptors
	Summary Points
	References
40
Brain Gene Expression in the Context of Nicotine Rewards: A Focus on Cholinergic Genes
	Introduction
	Clinical Examination of Cholinergic Gene Variation in Nicotine Addiction
	Preclinical Models Examining Cholinergic Gene Variation in Nicotine Addiction
	Other Potential Genes Underlying ND
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Genetic Techniques in Preclinical/Clinical Models
	Summary Points
	References
41
HIV-Infected Subjects and Tobacco Smoking: A Focus on Nicotine Effects in the Brain
	Introduction
	Nicotine From Smoking and Brain Nicotinic Acetylcholine Receptors
	Smoking Cessation Efforts in HIV-Infected Smokers
	Dependence and Prevalence of Smoking in HIV-Infected Individuals
	Smoking and Nicotine Consequences in HIV-Infected Individuals
	Cognition in HIV-Infected Smokers
	Mini Dictionary of Terms
	Key Facts About HAND
	Key Facts About Nicotine-Induced Upregulation of α4β2-nAChRs
	Summary Points
	References
42
Renin-Angiotensin System Genes and Nicotine Dependence
	Introduction
	Brain RAS Genes Might Contribute to Nicotine Dependence
	Conclusion and Future Remarks
	Implications for Treatments
	Mini-Dictionary of Terms
	Key Facts on the Renin-Angiotensin System (RAS)
	Summary Points
	References
43 Nicotine Dependence and the CHRNA5/CHRNA3/CHRNB4 Nicotinic Receptor Regulome
	Introduction: Tissue Expression and Function of Nicotinic α5, α3, β4 Subunits
	Proteins Regulating CHRNA5/CHRNA3/CHRNB4 Transcription
	Polymorphisms Regulating CHRNA5/CHRNA3/CHRNB4 mRNA Expression
	Epigenetics and Environmental Factors Regulating CHRNA5/CHRNA3/CHRNB4
	Clinical Associations With the CHRNA5/CHRNA3/CHRNB4 Regulome
	Mini-Dictionary of Terms
	Key Facts of Gene Expression
	Summary Points
	References
44
Brain, Nrf2, and Tobacco: Mechanisms and Countermechanisms Underlying Oxidative-Stress-Mediated Cerebrovascul ...
	Introduction
	Health Statistics
	Smokers: Health Management and Current Challenges
	Cerebrovascular Perspective: Smoking, Nicotine, and BBB
	The Nrf2 Pathway and Its Implications in TS-Induced Cerebrovascular Dysfunctions
	Targeting Nrf2 for Preventing Cigarette Smoke-Induced Cerebrovascular Dysfunctions
	Mini-Dictionary of Terms
	Key Facts of Tobacco Smoke
	Key Facts of Nicotine
	Key Facts of Nuclear Factor Erythroid 2-Related Factor (Nrf2)
	Summary Points
	References
45
Effects of Nicotine and Histone Deacetylase Inhibitors on the Brain
	Introduction
	Histone Acetylation and Deacetylation by Acetyltransferases and Deacetylases
		Histone Deacetylase Inhibitors
		Histone Deacetylase and Nicotine Effects on the Nervous System
			Nicotine Mimics the Action of HDAC Inhibitors
			Effect of HDACi and Nicotine on Memory
			Effects of HDACi on the Reinforcing Properties of Nicotine
	Applications to Treatments
	Mini-Dictionary of Terms
	Key Facts
	Summary Points
	References
46
L-Type Calcium Channels and Nicotine
	What Are L-Type Calcium Channels?
	The Relationship Between LTCCs and Nicotine Treatments
	Antinociception
	Locomotion
	Dependence
	Anxiety
	Cognitive Functions
	LTCCs Expression
	Firing Patterns
	Mini-Dictionary of Terms
	Key Facts of L-Type Calcium Channel (LTCC)
	Summary Points
	References
47
The Co-occurrence of Nicotine With Other Substance Use and Addiction: Risks, Mechanisms, Consequences, and Im ...
	Introduction
		The Vulnerability of Youth
		Increased Risk of Other Substance Use and Addiction
	The Neurobiological Underpinnings of Co-Occurring Nicotine and Other Substance Use and Addiction
		Nicotine and Alcohol
		Nicotine and Cannabis
		Nicotine and Cocaine
		Multiple Nicotine Product Use
	What Is Needed to Reduce Nicotine Use and Its Consequences
		Implications for Treatment
	Mini-Dictionary of Terms
	Key Facts about Nicotine's Relationship With Other Addictive Substances
	Summary Points
	References
48
Comorbid Smoking and Gambling Disorder: Potential Underlying Mechanisms and Future Explorations
	Introduction
	Underlying Mechanisms Involved in Co-morbid Smoking and Gambling
	Influence of Nicotine/Tobacco on Reinforced Behaviour
	Influence of Nicotine/Tobacco on Risk-Taking
	Influence of Nicotine/Tobacco on Gambling
	The Potential Influence of Gambling Behaviour on Tobacco Use
	Areas in Need of Future Exploration
	Mini-Dictionary of Terms
	Summary Points
	References
49
Neuroscience of Tobacco and Crack Cocaine Use: Metabolism, Effects, and Symptomatology
	Introduction
	Tobacco as a Gateway
	Smoke as Drug Abuse Potentiation
	Nicotine Mechanism of Action Associated to Cocaine
	Nicotine Molecular Mechanism in Combination With Cocaine
	Nicotine and Cocaine Dependence and Craving
	Nicotine and Cocaine Dependence Pharmacological Treatment
	Final Considerations
	Mini-Dictionary of Terms
	Key Facts of Nicotine and Cocaine Misuse
	Summary Points
	References
50
Salivary Cotinine Assays
	Introduction
	Methods of Analysis
	Recent Developments in Sample Pretreatment and Cotinine Determination
	Mini-Dictionary of Terms
	Summary Points
	References
51
Overview of Cotinine Cutoff Values for Smoking Status Classification
	Salivary Cotinine
	Serum Cotinine
	Urinary Cotinine
	Issues in Determining Cutoffs
	Drop in Cutoff Values Over the Last 20Years
	Mini-Dictionary of Terms
	Key Facts of Cutoff Value
	Summary Points
	References
52
Smoking Abstinence Expectancies Questionnaire
	Smoking: Prevalence and Global Impact
	Theoretical and Clinical Ties: Smoking Abstinence Expectancies and Smoking
	Measurement Development: Smoking Abstinence Expectancies Questionnaire
	Alternative Measures
	Future Directions
	Conclusion
	Mini-Dictionary of Terms
	Summary Points
	References
53
 Pharmacist-led Smoking Cessation Services: Current and Future Perspectives
	Introduction
	Different Settings of Pharmacist-led SCS
	Contributing Factors Leading to Successful Pharmacist-led SCS
	Future Developments of Pharmacist-led SCS
	Implications for Treatment
	Mini-Dictionary of Terms
	Key Facts of Pharmacist-led SCS
	Summary Points
	References
54
Nicotine Use and Weight Control in Young People: Implications for Prevention and Early Intervention
	Mechanisms Linking Weight Concerns and Weight Loss With Tobacco Use
		Metabolic Drivers
		Social Cognitive Drivers
		Social Ecological Frameworks
		Summary and Integration
	What Does the Recent Empirical Literature Tell Us?
		Cross-Sectional Research
		Longitudinal Research
		Summary and Integration
	Mini-Dictionary of Terms
	Key Facts About Smoking, Eating, and Weight Loss Control
	Summary Points
	References
55
Exercise as a Smoking Cessation Aid
	Introduction
	Why Exercise Might be an Effective Smoking Cessation Treatment Option
	Exercise as a Smoking Cessation Aid
	Future Directions
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of Exercise as a Smoking Cessation Aid
	Summary Points
	References
56
Varenicline: Treating Smoking Addiction and Schizophrenia
	Chronic Mental Illness: Schizophrenia
	Substance Related Disorders in the Schizophrenic Population
	Prevalence of Smoking Addiction in Schizophrenia
	Hypotheses of Smoking Addiction and Schizophrenia
	Varenicline, an Attractive Treatment Option for Smoking Addiction in Schizophrenia
	Other Aspects of Varenicline Use in Schizophrenic Patients
	Adverse Events and Varenicline Use in Patients With Schizophrenia
	Mini-Dictionary of Terms
	Key Facts of Smoking Addiction in Schizophrenic Patients
	Summary Points
	References
57
Nicotine Vaccines: The Past, the Present, and the Future
	Introduction: The Need of Developing Nicotine Vaccines
	The Past: The First-Generation Nicotine Vaccines
	The Present: Nanoparticle-Based Nicotine Vaccines
	The Future: Combining Previous Successes and Investigating New Concepts
	Mini-Dictionary of Terms
	Key Facts of Nicotine Vaccines
	Summary Points
	References
58
Treating Nicotine Dependence in Psychiatric Hospitals
	Introduction
	Smoking Among Persons With a Mental Disorder
		Smoking Prevalence and Health Burden
		Factors Associated With Elevated Smoking Rates Among Persons With a Mental Disorder
		A Smoking ``Culture´´
	Smoke-Free Policies in Psychiatric Hospitals
		Difficulties Implementing Smoke-Free Policies in Psychiatric Hospitals
		Prevalence of Treatment for Nicotine Dependence in Psychiatric Hospitals
	Improving Provision of Treatment for Nicotine Dependence in Psychiatric Hospitals
		A Systems-Change Approach
		Interventions to Increase the Provision of Treatment for Nicotine Dependence in Psychiatric Hospitals
	Continuation of Nicotine Dependence Treatment After Discharge From the Hospital
	Mini-Dictionary of Terms
	Key Facts of Treating Nicotine Dependence in Psychiatric Hospitals
	Summary Points
	References
59
Oral 18-Methoxycoronaridine (18-MC) Decreases Nicotine Self-Administration in Rats
	Introduction
	Methods
	Findings
	Discussion
	Conclusions
	Mini-Dictionary of Terms
	Key Facts
	Summary Points
	References
60
 Pharmacogenetics and Smoking Cessation
	Introduction
	Smoking Cessation Using Genetics of Drug Metabolizing Enzymes
		The Nicotine Metabolite Ratio
		CYP2A6 and Smoking Cessation
		CYP2B6 and Smoking Cessation
	Smoking Cessation Using Genetics of Central Nervous System Targets
		nAChR and Smoking Cessation
		Dopaminergic Pathway and Smoking Cessation
			DRD2
			COMT
			DRD4
			DAT
	Smoking Cessation Using Multiple Genetic Predictors
		CYP2A6 and nAChR Combined Genetic Risk Scores
		Additive Genetic Efficiency Score (AGES)
	Mini-Dictionary of Terms
	Key Facts of Pharmacogenetics
	Summary Points
	References
61
The Orexin System and Nicotine Addiction: Preclinical Insights
	Neuroanatomical and Molecular Interactions
		Acute Nicotine and Orexin
		Chronic Nicotine and Orexin
	Orexin as a Therapeutic Target for Nicotine Dependence
		Nicotine Self-Administration
		Reinstatement of Nicotine Seeking
		Withdrawal and Motivation
		Divergent Findings
	Human Studies
	Implications for Treatments
	Conclusion
	Mini-Dictionary of Terms
	Key Facts of the Orexin System
	Summary Points
	References
62
Tobacco Control Policies and Smokers Responses
	Introduction
	Adult Smoking Behavior
	Youth Smoking Behavior
	ETS Exposure
	Smoking-Related Health Outcomes
	Directions for Future Research
	Mini-Dictionary of Terms
	Key Facts
	Summary Points
	References
63
Resources for the Neuroscience of Nicotine
	Introduction
	Mini-Dictionary of Terms
	Key Facts
	Summary Points
	Acknowledgements (in alphabetical order)
	References
Index