Nicotine and Behavioral Sensitization

Department of Anesthesia and Critical Care, University of Chicago, MC4028, Chicago, IL 60637, USA.
Journal of Molecular Neuroscience (Impact Factor: 2.34). 09/2009; 40(1-2):154-63. DOI: 10.1007/s12031-009-9230-7
Source: PubMed


Use of tobacco products contributes to hundreds of thousands of premature deaths and untold millions of dollars in health care costs in this country each year. Nicotine is the principal neuroactive component in tobacco, but, despite ongoing research efforts, the cellular basis of its effects on behavior remains unclear. Efforts to resolve this conundrum have focused on the mesoaccumbens dopamine system, which contributes to the rewarding effects of many addictive drugs, including nicotine. The goal of this review is to outline recent advances and highlight some of the important unanswered questions regarding nicotine's effects on neuronal excitability and synaptic plasticity within the brain reward pathways.

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    • "Electrochemical measurements were conducted in the NAcc and VTA, two primary interrelated structures of the mesocorticolimbic motivation-reinforcement circuit (Wise and Bozarth 1987). Since the locomotor-activating effects of nicotine are rapidly enhanced or sensitized following repeated exposure (Clarke 1990; Domino 2001; Vezina et al. 2007; Mao and McGehee 2010), we also examined how nicotine-induced GLU responses change during repeated drug injections and how these neurochemical changes are related to changes in locomotion. "
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    ABSTRACT: Although numerous data suggest that glutamate (GLU) is involved in mediating the neural effects of nicotine, direct data on nicotine-induced changes in GLU release are still lacking. Here we used high-speed amperometry with enzyme-based GLU and enzyme-free GLU-null biosensors to examine changes in extracellular GLU levels in the ventral tegmental area (VTA) and nucleus accumbens shell (NAcc) induced by intravenous nicotine in a low, behaviorally active dose (30 μg/kg) in freely moving rats. Using this approach, we found that the initial nicotine injection in drug-naive conditions induces rapid, transient, and relatively small GLU release (~90 nM; latency ~15 s, duration ~60 s) that is correlative in the VTA and NAcc. Following subsequent nicotine injections within the same session, this phasic GLU release was supplemented by stronger tonic increases in GLU levels (100-300 nM) that paralleled increases in drug-induced locomotor activation. GLU responses induced by repeated nicotine injections were more phasic and stronger in the NAcc than in VTA. Therefore, GLU is phasically released within the brain's reinforcement circuit following intravenous nicotine administration. Robust enhancement of nicotine-induced GLU responses following repeated injections suggests this change as an important mediator of sensitized behavioral and neural effects of nicotine. This article is protected by copyright. All rights reserved.
    Full-text · Article · Sep 2013 · Journal of Neurochemistry
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    • "Nicotine, morphine, ethanol, and psychostimulant drugs, such as amphetamine and cocaine, could induce behavioral sensitization (B.S.) which is characterized by escalating psychomotor responses to repeated drug exposure (induction ) or an increased response to a drug after a period of abstinence (expression) (Robinson and Becker 1986; Mao and McGehee 2010; Steketee and Kalivas 2011). The mechanisms involved in such a phenomena have been extensively explored in animal models, and it has been accounted for neuroadaptations in the dopaminergic "
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    ABSTRACT: Behavioral sensitization (B.S.) is a pathophysiological animal model for stimulant-induced psychosis and addiction. Accumulated evidence indicates that inflammatory processes are involved in psychostimulants effects in the CNS. Cannabinoids like WIN55,212-2 act as potential activators of PPAR-γ and affects the inflammatory status of the CNS. The purpose of this study is to determine PPAR-γ role in induction and expression of B.S. and the coincident inflammatory responses developed by WIN55,212-2 (WIN). Using open-field test, locomotor activity was monitored in animals treated with intraperitoneal low-dose WIN single or repeated injections. Concurrent striatal COX-2 and TNF-α levels and PPAR-γ activity were determined by immunoblotting assay. Effects of concomitant chronic or acute PPAR-γ pharmacological inhibition (with GW9662) were then investigated on behavioral and biochemical variables. WIN enhanced locomotor activity and while administered chronically augmented cytosolic COX-2 and TNF-α and also PPAR-γ nuclear levels. GW9662 co-administration completely prevented the induction of sensitizing effects of chronic WIN and altered the inflammatory responses. However, the expression of B.S. was intensified with GW9662 as assessed by increased locomotion after WIN challenge following 48 h withdrawal. Neuroinflammation and locomotor excitability in animals received just a single-dose WIN were also escalated with GW9662. Our findings conclude that PPAR-γ could play different key roles during B.S. development by WIN. Although PPAR-γ is mostly known for neuroprotective and anti-inflammatory effects, our data indicate that it mediates the B.S. induction by chronic WIN. However, while the B.S. was induced, PPAR-γ could play a homeostatic role opposing the expressed B.S. escalation.
    Full-text · Article · Jun 2013 · Neuromolecular medicine
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    • "The VTA is modulated by excitatory glutamatergic inputs arising from the PFC, bed nucleus of the stria terminalis, amygdala, pontomesencephalic tegmental nuclei (Mao and McGehee, 2010), and by a large population of inhibitory GABAergic interneurons (Johnson and North, 1992; Theile et al., 2008) and afferents that arise from heterogeneous sources (Geisler and Zahm, 2005). There are several different nAChR subunits expressed in the VTA, some of which are the α3, α4, α5, α6, α7, β2, and β3 subtypes (Azam et al., 2002; Perry et al., 2002; Yang et al., 2009). "
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    ABSTRACT: Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.
    Full-text · Article · Nov 2012 · Frontiers in Molecular Neuroscience
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