Effects of nicotine withdrawal on central dopaminergic systems

Fung, Yiu K.; Schmid, Marian J.; Anderson, Todd M.; Lau, Yuen-Sum

doi:10.1016/0091-3057(95)02063-2

Cited by 102 publications

(58 citation statements)

References 43 publications

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“…Nicotine withdrawal is known to result in a hypoactive dopamine system (Fung et al, 1996;Epping-Jordan et al, 1998), which could explain why we found the ventral pallidum, an important meso-limbic dopamine projection site (Klitenick et al, 1992), to be activated by smoking stimuli only in the NON-ABS session. Higher plasma levels of nicotine during the nonabstinent scans could also explain the greater neural response to smoking cues in this state, since nicotine has a facilitatory effect on the dopaminergic response to salient stimuli (Rice and Cragg, 2004;Zhang and Sulzer, 2004).…”

Section: Discussionmentioning

confidence: 75%

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Effects of Expectancy and Abstinence on the Neural Response to Smoking Cues in Cigarette Smokers: an fMRI Study

McBride

Barrett

Kelly

et al. 2006

Neuropsychopharmacol

294

240

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Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.

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Section: Discussionmentioning

confidence: 75%

“…In particular, smoking withdrawal seems to be associated with a hypo-dopaminergic state in humans (Smolka et al, 2004) and animals (Fung et al, 1996;Epping-Jordan et al, 1998), which could lead to abnormal neural activity in areas implicated in cue-reactivity, in particular the DLPFC, ACC, and striatum.…”

Section: Introductionmentioning

confidence: 99%

Effects of Expectancy and Abstinence on the Neural Response to Smoking Cues in Cigarette Smokers: an fMRI Study

McBride

Barrett

Kelly

et al. 2006

Neuropsychopharmacol

294

240

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“…Navigation and exploration ( Figure 2) were not statistically different after withdrawal in saline and in nicotine animals, as there was no treatment effect neither for navigation (F (1,12) =1.05, NS) nor for exploration (F<1, NS). Within 30 minutes, there was a significant habituation for both navigation (F (5,60) =57.96, p<0.0001) and exploration (F (5,60) =25.02, p<0.0001) but no significant interaction treatment X habituation for either navigation (F (5,60) =1.1, p=0.37, NS) or exploration (F<1, NS).…”

Section: Introductionmentioning

confidence: 91%

“…Withdrawal from chronic use of nicotine also results in increased anxiety [14,15], and reduced locomotor activity [8,12,[16][17][18][19][20], although these last processes were altered either after higher doses of nicotine than the one we chose, or in rats instead of mice. We have therefore tested the effects of nicotine withdrawal, after the low dose administered, on locomotor activity and anxiety behaviours of the mouse.…”

Section: Introductionmentioning

confidence: 97%

“…We therefore expected to provide evidence regarding which of these behaviours are specifically affected by nicotine withdrawal. We chose to administer continuously a low dose of nicotine (2.4 mg/kg/day, as free-base), via osmotic mini-pumps, as it was previously shown that it is sufficient to produce nicotinic receptor up-regulation in the mouse [11] and to induce withdrawal syndrome in the rat [12]. In accordance with previous studies [7,8,10,12,13], we then used 1 mg/kg of mecamylamine to precipitate homogeneously the withdrawal the last day of mini-pump theoretical depletion.…”

Section: Introductionmentioning

confidence: 99%

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A low dose of nicotine is sufficient to produce nicotine withdrawal in mice

Morgane¹,

Sandra²,

Jean-Pierre³

et al. 2010

Health

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The objective of our study was to investigate whether the chronic administration of a low dose of nicotine can be followed by a withdrawal syndrome at cessation of nicotine delivery. Previous studies showed various results, depending in the doses of nicotine, species, ways of administration and behavioural paradigms, but all emphasized a withdrawal effect on some or all of the following spontaneous behaviours: grooming, rearing, body shake or tremor, body scratching, abdominal constriction, jumping. However, it is not clear which behaviour is exactly altered, as a global behavioural index is most frequently used. This is not clear either if anxiety modulates the behavioral expression of withdrawal or which factors contribute to its locomotors effect, if any. To distant-angle these processes, we scored each of these behaviours individually before nicotine exposure, during continuous nicotine delivery and at cessation of nicotine delivery after precipitated withdrawal by mecamylamine injection. We also measured locomotor activity and anxiety levels in the same animals. We used a low dose of nicotine (2.4 mg/kg/day as free base) that has been previously shown to produce nicotinic receptors up-regulation, both in the brain and in blood cells. With such a low dose, nicotine withdrawal didn't affect locomotion nor anxiety levels but increased the number of rearing, jumping, and marginally, body-scratching. Other behaviours, classically considered to contribute to withdrawal syndrome, were unaffected, e.g., grooming, body or forelimb shakes. Our results show that anxiety may be dissociated from the behavioural withdrawal syndrome. Also, the severity of the syndrome produced by nicotine withdrawal is qualitatively and quantitatively different from the one induced by other drugs of abuse and also by the one produced by nicotine at higher doses.

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