Society for Research on Nicotine and Tobacco as an Outgrowth of the 1988 Surgeon General's Report on Nicotine Addiction: Reflections of the Early Presidents.

Introduction: The Society for Research on Nicotine and Tobacco began in the United States as a scientific organization "to stimulate the generation and dissemination of new knowledge concerning nicotine and tobacco in all its manifestations." Now in its 30th year, the Society is taking on new challenges in tobacco control, nicotine vaping, product regulation, and public policy.

Aims And Methods: This Review describes the formative years of the Society from the perspective of researchers who were in leadership positions during that time, documenting how biobehavioral and clinical research in the first 10 years was a continuation of the scientific mission of the 1988 United States Surgeon General's Report on Nicotine Addiction and summarizing organizational innovations during each president's term of office.

Cocaine and nicotine research illustrates a range of hypocretin mechanisms in addiction.

Hypocretins (also known as orexins) are neuropeptides synthesized in the lateral hypothalamus and perifornical region and projecting widely throughout the brain. They play an important modulatory role in plasticity related to addictive behavior. Hypocretin signaling to the ventral tegmental area (VTA) promotes synaptic plasticity by potentiating glutamatergic inputs to dopamine neurons and is required for the plasticity induced by stimulant drugs like cocaine.

Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA.

Rationale: The hypocretin (hcrt) system has been implicated in addiction-relevant effects of several drugs, but its role in nicotine dependence has been little studied.

Objectives: These experiments examined the role of the hcrt system in nicotine reinforcement.

Methods: Rats were trained for nicotine self-administration (NSA) on fixed-ratio schedules.

Hypocretin mechanisms in nicotine addiction: evidence and speculation.

Background: The hypocretin/orexin system has been implicated in arousal mechanisms, sleep, and sleep disorders, including narcolepsy, and more recently in drug addiction. Theoretically, hypocretin (hcrt) mechanisms appear to be potential substrates for nicotine addiction: arousal and attentional mechanisms influence use and withdrawal symptoms, and hcrt systems overlap anatomically with a number of brain regions associated with nicotine addiction.

Objective: This review summarizes the studies that have examined hcrt mechanisms in the effects of nicotine and describes hcrt innervation of, and effects in, several brain regions implicated in nicotine addiction.

Neuronal nicotinic receptors as brain targets for pharmacotherapy of drug addiction.

Nicotine addiction and other forms of drug addiction continue to be significant public health problems in the United States and the rest of the world. Accumulated evidence indicates that brain nicotinic acetylcholine receptors (nAChRs) are a heterogenous family of ion channels expressed in the various parts of the brain. A growing body of preclinical studies suggests that brain nAChRs are critical targets for the development of pharmacotherapies for nicotine and other drug addictions.

Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats.

The nicotinic partial agonist varenicline (VCL) is a recently approved medication for the treatment of tobacco dependence, yet very little preclinical research on this drug has been published. The present experiment examined the nicotinic partial agonist properties of VCL and its parent compound, cytisine (CYT), in a nicotine discrimination assay. Rats were trained to discriminate nicotine (0.

Medication-related pharmacological manipulations of nicotine self-administration in the rat maintained on fixed- and progressive-ratio schedules of reinforcement.

Rationale: The use of animal models to study existing medications for smoking cessation can elucidate the mechanism(s) of action of cessation agents and further validate the models for medication development.

Objective: The objective of the study was to evaluate the response of nicotine self-administration (NSA) to pharmacological agents related to the smoking cessation medication bupropion and to nicotine dosing mimicking nicotine replacement on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement.

Materials And Methods: NSA was maintained at a nicotine dose of 30 microg/kg/infusion i.

Translational research in medication development for nicotine dependence.

A major obstacle to the development of medications for nicotine dependence is the lack of animal and human laboratory models with sufficient predictive clinical validity to support the translation of knowledge from laboratory studies to clinical research. This Review describes the animal and human laboratory paradigms commonly used to investigate the pathophysiology of nicotine dependence, and proposes how their predictive validity might be determined and improved, thereby enhancing the development of new medications.

Effects of the selective dopamine D3 receptor antagonist SB-277011A on the reinforcing effects of nicotine as measured by a progressive-ratio schedule in rats.

The dopamine D3 receptor is primarily localized within the mesocorticolimbic system, and may therefore have potential as a pharmacotherapeutic target for the treatment of drug dependence. Studies have shown that the selective dopamine D3 receptor antagonist SB-277011A reduces a variety of dependence-related behavioral effects of cocaine, alcohol and heroin. A previous study examining SB-277011A on nicotine self-administration using relatively low doses of the antagonist and a low response requirement for nicotine found no effect on drug-taking behavior per se, whereas reinstatement of nicotine-seeking was reduced.

Neuroadaptive changes in the mesoaccumbens dopamine system after chronic nicotine self-administration: a microdialysis study.

There is little evidence to date to indicate if mesoaccumbens dopamine function at the neurochemical level is altered during early abstinence from chronic i.v. nicotine self-administration.

Local perfusion of nicotine differentially modulates somatodendritic dopamine release in the rat ventral tegmental area after nicotine preexposure.

We examined the effects of nicotine perfusion into the ventral tegmental area (VTA) on extracellular dopamine (DA) levels in rats using in vivo microdialysis. Local perfusion with nicotine for 80 min (10-100 microM) modestly increased (approximately 105-131% of basal) the extracellular DA levels in the VTA of rats that had been pretreated with saline for 5 days. In animals that had been pretreated with nicotine for 5 days (0.

Effects of nicotine preexposure on sulpiride-induced dopamine release in the nucleus accumbens.

We examined the effects of nicotine preexposure or saline on dopamine release to sulpiride in the rat nucleus accumbens. Microdialysis was used to locally perfuse the sulpiride into the ventral tegmental area while sampling dopamine levels in the nucleus accumbens. The increase (130% and 165% of basal) in extracellular accumbens dopamine levels observed during ventral tegmental area perfusion for 80 min with 10-100 microM sulpiride in saline-treated animals was reduced (128% and 105% of basal) in nicotine-preexposed animals.

Effects of acute and chronic nicotine on somatodendritic dopamine release of the rat ventral tegmental area: in vivo microdialysis study.

The objectives of the present study were to examine the effects of acute and chronic nicotine on dopamine (DA) release in the ventral tegmental area (VTA) of Long-Evans rats using in vivo microdialysis. Systemic application of acute nicotine (0.1-0.

Nicotine patches and the subjective effects of cigarette smoking: a pilot study.

Twenty-five per cent of the North American population smoke cigarettes regularly. Twelve smokers (aged 19 to 55 years, Fagerström test score 3 to 10) participated in a double-blind, placebo controlled, counterbalanced study to determine the extent to which subjective effects of smoking are altered by nicotine delivered by transdermal patches. Subjects wore a placebo or 21 mg nicotine patch while abstaining from smoking for 48 h.

Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics.

Nicotine addiction is a complex behavioral phenomenon comprising effects on several neural systems. Recent studies have expanded initial observations that the actions of nicotine on dopaminergic systems increase dopaminergic activity and release, leading to nicotine-induced reinforcement. Indeed, the actions of nicotine on many systems, including brainstem cholinergic, GABAergic, noradrenergic, and serotonergic nuclei, may help to mediate nicotine effects related to addiction.

Pharmacological manipulations of the pedunculopontine tegmental nucleus in the rat reduce self-administration of both nicotine and cocaine.

Rationale: The pedunculopontine tegmental nucleus (PPTg) has been implicated in the self-administration of drugs, particularly nicotine, which acts directly through the PPTg in addition to targeting midbrain dopamine neurons. The direct action of nicotine in PPTg may be through GABAergic mechanisms that have been shown to influence nicotine self-administration preferentially compared to cocaine.

Objective: The purpose of these experiments was to examine several pharmacological manipulations that alter neuronal activity in the PPTg for their specificity or generality in nicotine versus cocaine reinforcement.

GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat.

Rationale: The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons.

Activation of 5-HT(2C) receptors reduces the locomotor and rewarding effects of nicotine.

Rationale: Various compounds believed to selectively interact with the 5-HT(2C) receptor have been demonstrated to alter the functioning of ascending dopamine systems. We postulated that this functional interaction may extend to the behavioural effects of drugs of abuse whose rewarding properties are critically dependent upon mesolimbic DA activity.

Objectives: The present studies focussed on interactions between 5-HT(2C) receptor function and behaviours either supported or induced by nicotine.

Acute subjective and physiological responses to smoking in adolescents.

Aims: To determine the topography of cigarette smoking and the subjective and physiological effects of abstinence and nicotine in adolescents who smoke on a daily versus a non-daily basis.

Design: Repeated measures experiment, non-blinded, involving a single test session.

Setting: Human psychopharmacology laboratory.

Effects of abstinence and smoking on information processing in adolescent smokers.

Rationale: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood.

Objectives: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers.

Methods: Subjects were 16 young novice smokers (five male, 11 female), ages 14-18 years.

Nicotine self-administration in animals as a dependence model.

Various animal models of nicotine dependence now exist. To study the positive reinforcing effects of nicotine, there are choices of animal species, strains, and operant paradigms to use. This manuscript describes the use of one particular paradigm, a model in which work is done by laboratory animals to obtain intravenous infusions of nicotine.

Nicotine-induced fos expression in the pedunculopontine mesencephalic tegmentum in the rat.

The aim of this study was to assess the effects of a single dose of nicotine (NIC, 0.3 or 1.0 mg/kg, s.

Evidence that nicotinic alpha(7) receptors are not involved in the hyperlocomotor and rewarding effects of nicotine.

Neuronal nicotinic receptors are comprised of combinations of alpha(2-9) and beta(2-4) subunits arranged to form a pentameric receptor. Currently, the principal central nervous system (CNS) subtypes are believed to be alpha(4)beta(2) and a homomeric alpha(7) receptor, although other combinations almost certainly exist. The identity of the nicotinic receptor subtype(s) involved in the rewarding effects of nicotine are unknown.

Response of nicotine self-administration in the rat to manipulations of mu-opioid and gamma-aminobutyric acid receptors in the ventral tegmental area.

Rationale: The mesolimbic dopamine system has been implicated in the reinforcing effects of nicotine, a drug which appears to act at least in part through the ventral tegmental area (VTA). Other neuronal elements in the VTA are important in drug reward. In particular, mu opioid receptors in the VTA have been shown to influence cocaine reinforcement.

The pedunculopontine tegmental nucleus and the role of cholinergic neurons in nicotine self-administration in the rat: a correlative neuroanatomical and behavioral study.

The objective of this study was to determine whether the pedunculopontine tegmental nucleus plays a role in the maintenance of nicotine self-administration, and whether the ascending cholinergic projection from this nucleus to midbrain dopamine neurons in the ventral tegmental area might be involved. Studies were done with rats trained to self-administer nicotine intravenously. Self-administration was examined before and after the pedunculopontine tegmental nucleus was lesioned with the ethylcholine mustard aziridinium ion, a selective cholinergic toxin.