Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats

Natividad, Luis A.; Tejeda, Hugo A.; Torres, Oscar V.; O’Dell, Laura E.

doi:10.1002/syn.20713

Cited by 56 publications

(70 citation statements)

References 49 publications

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“…Previous studies have shown that tonic DA activity is decreased in nicotine-dependent animals (18) and that precipitated withdrawal from chronic nicotine leads to decreased DA levels (38). Using defined electrophysiological methods to measure VTA DA activity (18,22), we confirmed and extended these results to dependent animals experiencing spontaneous withdrawal, showing that tonic DA activity is further decreased during withdrawal from chronic nicotine.…”

Section: Discussionsupporting

confidence: 74%

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

Grieder

George

Tan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Nicotine, the main psychoactive ingredient of tobacco smoke, induces negative motivational symptoms during withdrawal that contribute to relapse in dependent individuals. The neurobiological mechanisms underlying how the brain signals nicotine withdrawal remain poorly understood. Using electrophysiological, genetic, pharmacological, and behavioral methods, we demonstrate that tonic but not phasic activity is reduced during nicotine withdrawal in ventral tegmental area dopamine (DA) neurons, and that this pattern of signaling acts through DA D2 and adenosine A2A, but not DA D1, receptors. Selective blockade of phasic DA activity prevents the expression of conditioned place aversions to a single injection of nicotine in nondependent mice, but not to withdrawal from chronic nicotine in dependent mice, suggesting a shift from phasic to tonic dopaminergic mediation of the conditioned motivational response in nicotine dependent and withdrawn animals. Either increasing or decreasing activity at D2 or A2A receptors prevents the aversive motivational response to withdrawal from chronic nicotine, but not to acute nicotine. Modification of D1 receptor activity prevents the aversive response to acute nicotine, but not to nicotine withdrawal. This double dissociation demonstrates that the specific pattern of tonic DA activity at D2 receptors is a key mechanism in signaling the motivational effects experienced during nicotine withdrawal, and may represent a unique target for therapeutic treatments for nicotine addiction.negative reinforcement | place conditioning | burst firing | population activity | osmotic minipumps T obacco addiction is the leading avoidable cause of disease and premature death in North America (1). Of more than 3,000 chemicals present in tobacco smoke, nicotine is the main psychoactive ingredient responsible for tobacco addiction (2). Withdrawal from chronic nicotine is hypothesized to represent a powerful source of negative reinforcement that drives relapse and compulsive tobacco use (3); therefore, understanding the neurobiological substrates mediating the motivational properties of nicotine withdrawal is an important step in the development of new treatments for nicotine addiction. Current hypotheses suggest that nicotine withdrawal leads to a decrease in dopamine (DA) signaling in the brain (4) and that DA neurons exhibit two activity states, phasic and tonic, that mediate separate aspects of behavior (5-7).Nicotine acutely produces both aversive and positive motivational effects (8, 9) by activating the mesolimbic DA system (7, 10) as well as non-DAergic neural substrates (11,12). DA neurons exhibit burst-and population-firing activity that leads to phasic and tonic DA release, respectively (5-7). Burst-firing produces a fast and large phasic DA release that mainly activates postsynaptic DA D1 receptors (D1Rs), and population-firing produces a slower tonic DA release that mainly activates the higher affinity (13) DA D2 receptors (D2Rs) (5, 6). The phasic and tonic activities of DA neurons are though...

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Section: Discussionsupporting

confidence: 74%

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

Grieder

George

Tan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…11 Previous work has shown that dopamine levels are decreased in the NAcc during nicotine withdrawal. 20,21 We hypothesize that nicotine withdrawal activates stress systems in the NAcc, which decreases dopamine levels in this region. As an indirect assessment of changes in dopamine transmission in the NAcc, the present study compared changes in gene expression of dopamine receptors (Drd1, Drd2, and Drd3) during nicotine exposure and withdrawal.…”

Section: Original Investigationmentioning

confidence: 99%

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

Torres

Pipkin

Ferree

et al. 2015

Nicotine & Tobacco Research

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IntroductionTobacco use is the number one cause of preventable deaths in the United States. 1 Of particular concern is the high rate of tobacco use among women, who are more susceptible to the negative health consequences of long-term smoking than men. 2 As a result, tobacco use is believed to be a major contributing factor to health disparities in women. In spite of the magnitude of the problem, surprisingly little is known about the underlying biological factors that promote tobacco relapse in females.Much work has suggested that stress promotes tobacco use in women. For example, women report more negative mood states, such as depression, anxiety, and intense craving during smoking abstinence than men. [3][4][5] Women also use more tobacco products and display lower quit rates relative to men. 6 Furthermore, women report that they maintain tobacco use to relieve intense withdrawal symptoms that emerge during abstinence, and they claim more often than men that the anxiety-reducing effects of cigarettes are the main reason for smoking. [7][8][9] Preclinical studies have shown that the behavioral and biological consequences of nicotine withdrawal are greater in female versus AbstractIntroduction: Previous work led to our hypothesis that sex differences produced by nicotine withdrawal are modulated by stress and dopamine systems in the nucleus accumbens (NAcc). We investigated our hypothesis by studying intact females to determine whether the mechanisms that promote withdrawal are ovarian-hormone mediated. Methods: Female rats were ovariectomized (OVX) or received sham surgery (intact) on postnatal day (PND 45-46). On PND 60, they received sham surgery (controls) or were prepared with nicotine pumps. Fourteen days later, half of the rats had their pumps removed (nicotine withdrawal) and the other half received sham surgery (nicotine exposure). Twenty-four hours later, the rats were tested for anxiety-like behavior using the elevated plus maze and light/dark transfer procedures. The NAcc was then dissected for analysis of several genes related to stress (CRF, UCN, CRF-R1, CRF-R2, CRF-BP, and Arrb2) or receptors for dopamine (Drd1 and Drd2) and estradiol (Esr2). Results: During withdrawal, intact females displayed an increase in anxiety-like behavior in both tests and CRF, UCN, and Drd1 gene expression. During nicotine exposure, intact females displayed a decrease in CRF-R1, CRF-R2, Drd3, and Esr2 gene expression and an increase in CRF-BP. This pattern of results was absent in OVX females. Conclusions: Nicotine withdrawal produced an increase in anxiety-like behavior and stress-associated genes in intact females that is distinct from changes produced by nicotine exposure. The latter effects were absent in OVX females, suggesting that stress produced by withdrawal is ovarianhormone mediated. These findings have important implications towards understanding tobacco use liability among females.

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“…Our results are consistent with previous studies in rats showing that nicotine pretreatment increased cocaine-induced reinforcement (McQuown et al, 2007) as well as locomotor sensitization (McQuown et al, 2009) in adolescent but not adult rats. Interestingly, nicotine withdrawal has been shown to differentially regulate extracellular levels of accumbal dopamine in adolescent versus adult rats (Natividad et al, 2010). Likewise, the rewarding actions of nicotine are more pronounced in adolescence compared to adult rats (Natividad et al, 2013).…”

Section: Pk Singh K Lutfymentioning

confidence: 99%

“…Research in the past has shown that nicotine use is initiated during adolescent period and proceeds to the use and abuse of other drugs (Best et al, 2000;Businelle et al, 2013;Carmody et al, 1985;DiFranza and Guerrera, 1990;Lisha et al, 2014;McKee et al, 2011;Rimm et al, 1995;Romberger and Grant, 2004;Torabi et al, 1993;York and Hirsch, 1995). This period of life is a very sensitive age in which the negative affective state associated with nicotine withdrawal is reduced while the rewarding action of nicotine is enhanced compared to adults (Carcoba et al, 2014;Dickson et al, 2014;Dickson et al, 2011;Hutchison and Riley, 2008;Lee et al, 2015;McQuown et al, 2009;Natividad et al, 2012;Natividad et al, 2010;Natividad et al, 2013;O'Dell et al, 2004;O'Dell et al, 2006;O'Dell et al, 2007;Shram et al, 2008;Torres et al, 2008;Wilmouth and Spear, 2004), making adolescents a vulnerable target to nicotine use and abuse as well as for use of other addictive drugs during adulthood. Consistent with this notion, previous studies have shown that nicotine exposure during adolescence can prime the use and abuse of cocaine, alcohol, and other addictive substances (Bechtholt and Mark, 2002;DiFranza and Guerrera, 1990;Horger et al, 1992;Hutchison and Riley, 2008;Kandel and Kandel, 2015;Kandel and Kandel, 2014;Kelley and Rowan, 2004;Kouri et al, 2001;Levine et al, 2011;…”

Section: Introductionmentioning

confidence: 99%

“…This period of life is a very sensitive age in which the negative affective state associated with nicotine withdrawal is reduced while the rewarding action of nicotine is enhanced compared to adults (Carcoba et al, 2014;Dickson et al, 2014;Dickson et al, 2011;Hutchison and Riley, 2008;Lee et al, 2015;McQuown et al, 2009;Natividad et al, 2012;Natividad et al, 2010;Natividad et al, 2013;O'Dell et al, 2004;O'Dell et al, 2006;O'Dell et al, 2007;Shram et al, 2008;Torres et al, 2008;Wilmouth and Spear, 2004), making adolescents a vulnerable target to nicotine use and abuse as well as for use of other addictive drugs during adulthood. Consistent with this notion, previous studies have shown that nicotine exposure during adolescence can prime the use and abuse of cocaine, alcohol, and other addictive substances (Bechtholt and Mark, 2002;DiFranza and Guerrera, 1990;Horger et al, 1992;Hutchison and Riley, 2008;Kandel and Kandel, 2015;Kandel and Kandel, 2014;Kelley and Rowan, 2004;Kouri et al, 2001;Levine et al, 2011;Li et al, 2014;McQuown et al, 2007;McQuown et al, 2009;Meliska et al, 1995;Natividad et al, 2010;Rinker et al, 2011;Rosenberg, 2014;Schindler et al, 2012;Schneider et al, 2012). There is also evidence showing that about 90% of regular smokers start using tobacco at an early age, and that early onset smoking carries a major risk for the development of addiction to other drugs of abuse (Rimm et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice

Singh

Lutfy

2017

Pharmacology Biochemistry and Behavior

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Previous preclinical studies have shown that nicotine pretreatment during adolescence increases the reinforcing actions of cocaine. However, little is known about the effect of prior nicotine administration on cocaine-induced conditioned place preference (CPP) and its reinstatement in adult mice. Besides, little information is available regarding the role of sex in this cross-talk between nicotine and cocaine. Thus, we examined if nicotine administration during adulthood would differentially alter cocaine-induced CPP, its extinction and reinstatement in male versus female mice and if the dose of nicotine was important in this regard. To this end, mice were pretreated with saline or nicotine (0.25 or 1 mg/ kg; twice daily for seven days) and then tested for place preference before and after single and repeated conditioning with cocaine (15 mg/kg). Mice were then exposed to extinction training and tested for reinstatement of CPP. Our results showed that male and female mice pretreated with saline and conditioned with cocaine each exhibited a robust CPP after a single cocaine conditioning. However, this response was blunted in mice pretreated with the lower but not higher dose of nicotine. Female mice pretreated with the lower dose nicotine also failed to show CPP after repeated conditioning. Reinstatement of cocaine-induced CPP was also blunted in these mice compared to their respective controls. Together, these results suggest that nicotine administration during adulthood exerts differential effects on cocaine-induced CPP and its reinstatement in male and female mice and the dose of nicotine is important in this regard.

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Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats

Cited by 56 publications

References 49 publications

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

Phasic D1 and tonic D2 dopamine receptor signaling double dissociate the motivational effects of acute nicotine and chronic nicotine withdrawal

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice

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