Archival ReportNicotine Withdrawal Increases Threat-Induced Anxiety but Not Fear: Neuroadaptation in Human Addiction
Section snippets
Participants
One hundred seventeen chronic smokers aged 18 or older completed one of two separate experiments (Table 1 provides description of participant characteristics). All participants reported ≥10 cigarettes/day ≥1 year, Fagerström Test for Nicotine Dependence (FTND) (21) score ≥4, and expired air carbon monoxide (CO) level ≥10 ppm during screening session. Startle nonresponders (resting startle response during screening session <4 μV) were excluded. All participants were compensated $20/hour for time
Results
Data analysis and figure preparation were accomplished with R (26, 27).
Discussion
Across two experiments, we provide evidence that startle response potentiation during unpredictable threat may be a biomarker of these stress neuroadaptations among human smokers in nicotine withdrawal. In addition, contrast of results for startle response potentiation across unpredictable versus predictable shock experiments provides preliminary evidence that these stress system neuroadaptations manifest selectively as increased anxiety during unpredictable or otherwise uncertain threat.
Limitations and Future Directions
Important limitations of this study will direct our near-term future research. Unpredictable and predictable shock manipulations were implemented in separate experiments because of concerns about carryover of putatively long-lasting anxious affect that precluded counterbalanced, within-subject manipulation. We recognize that this decision limits the strength of conclusions regarding differential nicotine deprivation effects during uncertain versus certain threat. However, the conclusion about a
References (51)
- et al.
Anxiogenic effects of high illumination levels assessed with the acoustic startle response in rats
Biol Psychiatry
(1997) - et al.
Darkness facilitates the acoustic startle reflex in humans
Biol Psychiatry
(1997) - et al.
Role of the bed nucleus of the stria terminalis versus amygdala in fear, stress, and anxiety
Eur J Pharmacol
(2003) - et al.
Fear-potentiated startle to threat, and prepulse inhibition among young adult nonsmokers, abstinent smokers, and nonabstinent smokers
Biol Psychiatry
(2007) - et al.
Initiation of cigarette smoking and subsequent smoking behavior among U.S. high school students
Prev Med
(1999) - et al.
Increased anxiety-like behavior in adult rats exposed to nicotine as adolescents
Pharmacol Biochem Behav
(2003) - et al.
Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppresses heroin self-administration in dependent rats
Brain Res
(2000) - et al.
Stress-induced relapse to heroin and cocaine seeking in rats: A review
Brain Res Rev
(2000) - et al.
Neurocircuitry of addiction
Neuropsychopharmacology
(2010) - et al.
An opponent-process theory of motivation: Temporal dynamics of affect
Psychol Rev
(1974)
Addiction and the brain antireward system
Annu Rev Psychol
The role of neuroadaptations in relapse to drug seeking
Nat Neurosci
Compulsive drug-seeking behavior and relapse: neuroadaptation, stress, and conditioning factors
Ann NY Acad Sci
Addiction motivation reformulated: An affective processing model of negative reinforcement
Psychol Rev
Neural systems involved in fear and anxiety measured with fear-potentiated startle
Am Psychol
Acoustic startle reflex in rhesus monkeys: a review
Rev Neurosci
Models and mechanisms of anxiety: Evidence from startle studies
Psychopharmacology
Sex differences in negative affect response during nicotine withdrawal
Psychophysiology
Alcohol selectively reduces anxiety but not fear: Startle response during unpredictable versus predictable threat
J Abnorm Psychol
Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs. anxiety
Neuropsychopharmacology
Corticotropin-releasing factor potentiates acoustic startle in rats: Blockade by chlordiazepoxide
Psychopharmacology
Corticotropin-releasing factor: Long-lasting facilitation of the acoustic startle reflex
J Neurosci
Anxious responses to predictable and unpredictable aversive events
Behav Neurosci
Tobacco withdrawal and negative affect: An analysis of initial emotional response intensity and voluntary emotion regulation
J Abnorm Psychol
Appetitive nature of drug cues confirmed with physiological measures in a model using pictures of smoking
Psychopharmacology
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2017, Drug and Alcohol DependenceCitation Excerpt :Our AUD groups, however, had higher rates of lifetime SUD and recent substance abuse than the non-AUD groups and although we statistically adjusted for SUD in our analyses, it is possible that the results are not specific to AUD and reflect a broader vulnerability for substance consumption. In fact, other studies have shown that heavy marijuana users (Hefner et al., 2017 unpublished results) and smokers experiencing acute nicotine deprivation (Hogle et al., 2010) display increased startle potentiation to U-threat but not P-threat. It has also recently been argued that heightened reactivity to U-threat reflects a neuroadaptation that emerges as a consequence of drug and alcohol exposure rather than a vulnerability factor (Kaye et al., 2017).