Nicotine as a typical drug of abuse in experimental animals and humans

Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
Psychopharmacology (Impact Factor: 3.88). 04/2006; 184(3-4):367-81. DOI: 10.1007/s00213-005-0155-8
Source: PubMed


Tobacco use through cigarette smoking is the leading preventable cause of death in the developed world. Nicotine, a psychoactive component of tobacco, appears to play a major role in tobacco dependence, but reinforcing effects of nicotine often are difficult to demonstrate directly in controlled laboratory studies with animal or human subjects.
To review the major findings obtained with various procedures developed to study dependence-related behavioral effects of nicotine in experimental animals and humans, i.e., drug self-administration, conditioned place preference, subjective reports of nicotine effects and nicotine discrimination, withdrawal signs, and ratings of drug withdrawal.
Nicotine can function as an effective reinforcer of drug-seeking and drug-taking behavior both in experimental animals and humans under appropriate conditions. Interruption of chronic nicotine exposure produces withdrawal symptoms that may contribute to relapse. Difficulties encountered in demonstrating reinforcing effects of nicotine under some conditions, relative to other drugs of abuse, may be due to weaker primary reinforcing effects of nicotine or to a more critical contribution of environmental stimuli to the maintenance of drug-seeking and drug-taking behavior with nicotine than with other drugs of abuse. Further experiments are also needed to delineate the role other chemical substances inhaled along with nicotine in tobacco smoke play in sustaining smoking behavior.
Nicotine acts as a typical drug of abuse in experimental animals and humans.

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    • "Stressful conditions and negative life events facilitate the initiation and maintenance of tobacco smoking (Anda et al., 1999; Morissette et al., 2007) and can alter the behaviour of tobacco addicted individuals by increasing the drug intake and the urge to smoke, as well as precipitating the relapse to smoking behavior (Todd, 2004). Nicotine, the major psychoactive component of tobacco smoke, is considered to be the key compound mediating the primary reinforcement stimulus leading to tobacco addiction (Le Foll and Goldberg, 2006). "
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    ABSTRACT: Stress is well known to affect responsiveness to drugs of abuse and influencing approaching and drug-taking behaviour in both animals and humans. Consistently, in nicotine addicted subjects both negative events and perceived stress levels are reported to increase drug use and facilitate relapse to smoke even after long periods of abstinence. It has been suggested that stressful stimuli may influence the rewarding properties of abused drugs by acting on the dopaminergic mesolimbic system. In line with this hypothesis, a recent microdialysis study in rats has shown that acute restraint stress exposure prevents the nicotine-induced mesolimbic dopaminergic activation in the nucleus accumbens (NAC) shell via a corticosterone-mediated mechanism. In the present study we sought to evaluate the impact of acute restraint stress on nicotine-induced activation of the mesoaccumbal dopaminergic system by extracellular single unit recordings of antidromically-identified NAC shell projecting dopaminergic neurons within the Ventral Tegmental Area (VTA). Nicotine intravenous administration dose-dependently (0.05–0.4 mg/kg) stimulated the spontaneous firing and bursting of mesoaccumbal dopaminergic neurons in unstressed rats, as previously reported. By contrast, nicotine failed to increase mesoaccumbal dopaminergic neuron activity in rats previously exposed to one-hour immobilisation stress. Our observations show that acute restraint stress inhibits the response of the mesoaccumbal dopaminergic system to the stimulating properties of nicotine. These findings corroborate the notion that stress reduces the sensitivity to nicotine and suggest that the decreased dopaminergic release in the NAC shell is due to a reduced firing and bursting activity in the VTA.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2014; 24(7). DOI:10.1016/j.euroneuro.2014.01.003 · 4.37 Impact Factor
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    • "Nicotine is considered as the major addictive component of tobacco smoke, resulting in addiction in humans [1,2]. According to the World Health Organization, nicotine addiction is a global health problem affecting one-third of the population [3]. "
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    ABSTRACT: Nicotine is rapidly absorbed from cigarette smoke and therefore induces a number of chronic illnesses with the widespread use of tobacco products. Studies have shown a few cerebral metabolites modified by nicotine; however, endogenous metabolic profiling in brain has not been well explored. H NMR-based on metabonomics was applied to investigate the endogenous metabolic profiling of brain hippocampus, nucleus acumens (NAc), prefrontal cortex (PFC) and striatum. We found that nicotine significantly increased CPP in mice, and some specific cerebral metabolites differentially changed in nicotine-treated mice. These modified metabolites included glutamate, acetylcholine, tryptamine, glucose, lactate, creatine, 3-hydroxybutyrate and nicotinamide-adenine dinucleotide (NAD), which was closely associated with neurotransmitter and energy source. Additionally, glutathione and taurine in hippocampus and striatum, phosphocholine in PFC and glycerol in NAc were significantly modified by nicotine, implying the dysregulation of anti-oxidative stress response and membrane metabolism. Nicotine induces significant metabonomic alterations in brain, which are involved in neurotransmitter disturbance, energy metabolism dysregulation, anti-oxidation and membrane function disruptions, as well as amino acid metabolism imbalance. These findings provide a new insight into rewarding effects of nicotine and the underlying mechanism.
    BMC Neuroscience 02/2014; 15(1):32. DOI:10.1186/1471-2202-15-32 · 2.67 Impact Factor
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    • "Nicotine is a weak primary reinforcer—in pre-clinical models, intravenous nicotine infusions support very low levels of operant behavior that are easily reversed (Le Foll and Goldberg 2006; Palmatier et al. 2007a). However, nicotine has potent reinforcement-enhancing effects (Caggiula et al. 2009)— nicotine administration robustly increases responding for other drug and non-drug reinforcers (Donny et al. 2003). "
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    ABSTRACT: RATIONALE: Nicotine (NIC) potently increases operant responding for non-NIC reinforcers, and this effect may depend on drug-mediated increases in incentive motivation. According to this hypothesis, NIC should also potently increase approach to Pavlovian-conditioned stimuli associated with rewards. OBJECTIVE: The present studies explored the effects of NIC on Pavlovian-conditioned approach responses. METHOD: To do so, liquid dippers were used to deliver an unconditioned stimulus (US; 0.1 ml sucrose) after presentation of a conditioned stimulus (CS; 30 s illumination of a stimulus light)-both the CS and US were presented in receptacles equipped to monitor head entries. RESULTS: In experiment 1, the CS and US were presented in the same receptacle, but NIC pretreatment (0.4 mg/kg base) did not increase conditioned approach responses. Delivery of the sucrose US was then shifted to receptacle in a different location. All rats learned to approach the new US location (goal-tracking) at similar rates. Approach to the CS receptacle (sign-tracking) declined for saline-pretreated rats, but NIC pretreatment increased sign-tracking. In experiment 2, NIC pretreatment increased sign-tracking when the CS and US were spatially separated during acquisition. In experiment 3, NIC pretreatments were replaced with saline, but the effect of NIC persisted for an additional 24 test sessions. CONCLUSION: The findings suggest that NIC increases incentive motivation and that this effect is long-lasting, persisting beyond the pharmacological effects of NIC.
    Psychopharmacology 10/2012; 226(2). DOI:10.1007/s00213-012-2892-9 · 3.88 Impact Factor
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