Cue Exposures Research Articles

Trauma cue-elicited emotional response profiles influence acute experiences of alcohol urge

Background and objectivesAffective responses to trauma cues in individuals with posttraumatic stress (PTS) can evoke a desire to drink and may shed light on novel mechanisms of PTS-drinking. The present study aimed to (1) identify and characterize patterns of acute emotional responses (ER) to trauma cues and (2) examine how these patterns influence drinking urge. MethodsUniversity students (N = 304; Mage = 19; 52.3% female) completed a structured clinical interview to confirm trauma history and PTS. At an experimental session one week later, participants completed a series of three trauma cue exposures. Affect and drinking urge were measured at baseline, after each cue exposure, and at experiment's end. ResultsLatent profile analysis of ER yielded a five-profile solution: (1) Nonresponders (2) Low Responders (3) Moderate Responders (4) Resilient Responders and (5) High Responders. Profiles differed by trait neuroticism, PTS, and emotion dysregulation, with High Responders as the most severe group. In latent growth curve models, profiles significantly predicted alcohol urge trajectories in a graded pattern. High Responders, with the greatest affective intensity, showed the strongest urge. Duration of affect was also implicated with Resilient Responders, who had similar intensity but faster overall affective recovery time compared to High Responders, demonstrating lower mean levels of urge. LimitationsExternal validity is limited. ConclusionsIndividual differences in ER to trauma cues are important for understanding alcohol urge. Findings can inform integrative treatments for PTS-drinking by targeting ER to shorten affective recovery to trauma reminders and reduce the need for alcohol use as a regulation strategy.

ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder–Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial

IntroductionAlthough alcohol dependence (AD) is highly prevalent, only few medications are approved for its treatment. While currently approved medications, such as naltrexone (NTX), reduce craving and relapse risk to a...

Heart Rate Variability, Cue-Evoked Ventromedial Prefrontal Cortical Response, and Problem Alcohol Use in Adult Drinkers

BackgroundMany studies employed cue exposure paradigms to investigate the neural processes underlying cue-elicited alcohol craving. Cue exposure elicits robust autonomic reactivity. However, whether or how cue-elicited autonomic response relates to the severity of alcohol misuse and the neural bases underlying the potential relationship remain unclear. MethodsWe examined cue-related brain activations in association with heart rate variability, as indexed by the root mean square of the successive differences (RMSSD), during alcohol versus neutral cue blocks in 50 adult alcohol drinkers (24 men). Imaging and heart rate variability data were collected and processed with published routines. Mediation analyses were conducted to examine the interrelationship between regional activities, cue-elicited changes in RMSSD, and the severity of problem alcohol use, as assessed with the Alcohol Use Disorders Identification Test (AUDIT). ResultsThe results showed higher RMSSD during alcohol than during neutral cue exposures, with alcohol (vs. neutral) cue-evoked RMSSD positively correlated with AUDIT score. Further, alcohol (vs. neutral) cue-elicited activity in the ventromedial prefrontal cortex was negatively correlated both with increases in RMSSD and with the AUDIT score. Mediation analyses suggested that the RMSSD mediated the relationship between ventromedial prefrontal cortex cue activity and the AUDIT score. ConclusionsThese findings substantiate the neural correlates of the presumably parasympathetic response during alcohol cue exposure and the interrelationship among ventromedial prefrontal cortex activity, autonomic response, and problem alcohol use.

Executive Functioning Moderates Responses to Appetitive Cues: A Study in Severe Alcohol Use Disorder and Alcoholic Liver Disease.

To examine subjective and psychophysiological responses to appetitive cues during an alcohol cue reactivity task, and its relation to alcoholic liver disease and assess whether executive functioning is associated with appropriate regulation of cue-elicited responses in individuals with severe alcohol use disorder (AUD). Seventeen treatment-seeking alcoholic liver disease patients and a control group of treatment-seeking severe AUD participants completed neuropsychological executive functioning measures (Stroop task; Trail-making test) and the cue reactivity task, whereby control (water) and alcohol beverage cues were presented, followed by respective recovery periods. Subjective alcohol craving and heart rate variability were recorded across the task. Overall cue reactivity and consequent recovery after cue offset during the cue reactivity task was observed, and alcoholic liver disease participants demonstrated a reduced overall recovery effect. Better Stroop performance related to greater overall and alcohol-specific cue reactivity within the control AUD group, and alcoholic liver disease participants showed dysfunctional activity regardless of executive functioning performance. No group differences in recovery effects according to executive functioning performance were seen. Among patients with AUD, having alcoholic liver disease seems to reduce overall regulation of responses to eliciting cues. Executive functioning moderated the magnitude of responses during cue exposures in our AUD sample overall; having alcoholic liver disease did not appear to affect regulation related to executive functioning during recovery.

P.1.g.058 - The effect of chronic variable stress on amphetamine sensitization in high and low sucrose consuming rats

In drug dependence studies, rats are often tested daily with short breaks (such as weekends) spent untested in their home cages. Research on alcohol models has suggested that breaks from continuous testing can transiently enhance self-administration (termed the “alcohol deprivation effect”). The present study explored whether the salience of cocaine-access cues is increased after skipping weekend cocaine and cue exposures. Ultrasonic vocalizations (USVs) of the 50-kHz class are emitted by rats exposed to intravenous cocaine and have been shown to increase with repeated drug exposure at the same dose level (sensitization). The present study found that over the course of several weeks of cocaine self- or yoked-administration pre-drug cues signaling forthcoming access or delivery of cocaine elicited marked amounts of anticipatory 50-kHz USVs, and that weekend deprivation from cues and cocaine exaggerated further the level of calling (more calls on Mondays compared to Fridays). Anticipatory USVs extinguished less rapidly when weekend access to unreinforced cues was denied. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and resistance to extinction.

Effects of repeated cue exposure on cannabis craving

OF THESIS EFFECTS OF REPEATED CUE EXPOSURE ON CANNBIS CRAVING Craving is a key element of the cannabis withdrawal syndrome that has been associated with continued use and relapse. Although cue-induced cannabis craving has been established in single laboratory sessions, procedures to sustain craving over multiple sessions are needed. The purpose of the present study was to determine if cue-induced craving responses could be elicited in the same subjects across multiple sessions. It was hypothesized that exposure to cannabis cues would produce more robust craving responses than exposure to neutral cues and that elicited craving responses will be sustained across multiple cue exposures. Five experimental cue exposure sessions (1 neutral and 4 cannabis) were conducted. Craving was assessed with the Marijuana Craving Questionnaire (MCQ) Short Form, Visual Analog Scale (VAS), Subject-Rated Physiological Questionnaire, blood pressure, and heart rate. Results revealed significant effects of initial cannabis cue exposure on VAS craving responses and Subject-Rated Physiological measures relative to the neutral cue exposure condition. No significant differences were found on MCQ composite scores or physiological measures. Craving responses following initial cannabis cue exposure were not maintained across sessions. There is a need for a better understanding of the factors that contribute to continued drug use despite quit attempts.

Comparison of Craving Between Smoked and Smokeless Tobacco Across a Variety of Cue Exposures

Smokeless tobacco use is a major health issue but has received less attention in craving research. The present non-funded study aimed to assess craving associated with smokeless tobacco compared to smoked forms. Forty-eight nicotine dependent male subjects attending a deaddiction center in India were recruited. The subjects were exposed to six nicotine related and two control cues in random order for variable time durations. The urge to consume the tobacco product was rated. Tobacco-related cues produced different patterns and degrees of craving among users of smoked and smokeless tobacco. This has implications for management and drug development.

Cue-Induced Cigarette Cravings and Smoking Cessation: The Role of Expectancies

Cue-induced cigarette cravings have been oft studied as potentially important predictors of smoking cessation outcomes. The literature on the relationship between cue-induced cravings and cessation, however, remains mixed. One possible explanation for the discrepant results in the literature may be the as-yet untested variability in expectancies of craving. Indeed, as with many interoceptive responses, cravings and their downstream consequences may be influenced by expectancies. To date, no study has examined the influence of expected cravings following smoking cue exposures on actual craving experiences and cessation outcomes. The objective of this study, therefore, was to test the possibility that smokers' expected craving levels in response to smoking cues would be related to actual cravings following cue exposure and that expected cravings would be related to cessation outcomes. Nicotine-dependent adult smokers (n = 153) were exposed to sets of neutral and smoking cues and completed questionnaires assessing (a) prior to the exposures, the cigarette craving levels they expected to experience following the cue exposures and (b) following the exposures, their actual craving levels. Participants also reported the duration of their most recent quit attempt and their perceived future quit difficulty. Findings indicated that expected cravings assessed prior to the cue exposures were significantly related to actual cravings following the exposures. In addition, both expected cravings and actual cravings were related to shorter previous quit duration and higher perceived quit difficulty. Study results highlight the importance of considering both expected and actual cravings in cue-induced craving paradigms.

D‐cycloserine facilitates extinction of cocaine self‐administration in c57 mice

Cocaine is a highly addictive drug of abuse for which there are currently no medications. In rats and mice d-cycloserine (DCS), a partial NMDA agonist, accelerates extinction of cocaine seeking behavior. Since cues delay extinction here, we evaluated the effects d-cycloserine in extinction with and without the presence of cues. Two doses of DCS (15 and 30 mg/kg) were studied in C57 mice. Mice self-administered cocaine (1 mg/kg) for 2 weeks and then underwent a 20-day extinction period where DCS was administered i.p. immediately following each daily session. Extinction was conducted in some mice with the presence of cocaine-paired cues; while others were in the absence of these cues. DCS treated mice (either dose) showed significantly reduced lever pressing during extinction with cue exposures when compared with vehicle treated mice. Without cues, animals showed much lower levels of lever pressing but the differences between vehicle and DCS were not significant. DCS accelerated extinction with the presence of cues, but there were no differences on extinction without cues as compared with vehicle. These findings are consistent with DCS disrupting the memory process associated with the cues. Since drug cues are significantly involved in relapse, these findings support research to assess the therapeutic potential of DCS in cocaine addiction.

Exposure to smoking cues: Cardiovascular and autonomic effects

Laboratory exposures to smoking cues have been shown to reliably induce self-reported cigarette cravings among smokers, a model of environmentally triggered urges to smoke that can contribute to poorer cessation success. Several studies have also demonstrated that cue exposures give rise to changes in heart rate and blood pressure. Few studies, however, have investigated possible cue effects on heart rate and blood pressure variability (HRV and BPV). Particularly intriguing in this regard are cardiac oscillations in the low (i.e., 0.04–0.15 Hz), and high (i.e., 0.15–0.50 Hz) frequency range, which are thought to reflect components of autonomic control and response to environmental challenges. A closer examination of cardiovascular reactivity may thus help characterize the autonomic response to smoking cue exposure. To that end, an experimental study was conducted in which nicotine dependent daily smokers ( n = 98) were exposed to guided imagery of neutral and smoking situations, while continuous, noninvasive, beat-to-beat cardiovascular data were collected. Consistent with previous research, the findings revealed significant increases in both systolic and diastolic blood pressure during smoking imagery, relative to neutral imagery. In addition, power spectral density analyses of heart rate and blood pressure variability revealed elevated HRV and BPV in both the low- and high-frequency ranges during the smoking imagery. The results suggest the presence of an autonomic component to smoking cue reactivity, and also raise the possibility of long-term negative cardiac consequences for smokers who ubiquitously encounter cues in their daily environments.

Cocaine deprivation effect: Cue abstinence over weekends boosts anticipatory 50-kHz ultrasonic vocalizations in rats

In drug dependence studies, rats are often tested daily with short breaks (such as weekends) spent untested in their home cages. Research on alcohol models has suggested that breaks from continuous testing can transiently enhance self-administration (termed the “alcohol deprivation effect”). The present study explored whether the salience of cocaine-access cues is increased after skipping weekend cocaine and cue exposures. Ultrasonic vocalizations (USVs) of the 50-kHz class are emitted by rats exposed to intravenous cocaine and have been shown to increase with repeated drug exposure at the same dose level (sensitization). The present study found that over the course of several weeks of cocaine self- or yoked-administration pre-drug cues signaling forthcoming access or delivery of cocaine elicited marked amounts of anticipatory 50-kHz USVs, and that weekend deprivation from cues and cocaine exaggerated further the level of calling (more calls on Mondays compared to Fridays). Anticipatory USVs extinguished less rapidly when weekend access to unreinforced cues was denied. The results may have clinical implications, in that intermittently avoiding cues or context may enhance drug cue salience and resistance to extinction.

An analysis on cue-induced craving and the related factors among heroin dependence

Objective To understand the cue-induced craving, physiological reactions to heroin-related cues, and to explore the factors that impact the cue-induced craving. Methods 369 abstinent heroin addicts were exposed to videotapes of heroin using and simulacrum after the self relaxation. The craving, abstinent symp-toms were measured before and after cue exposures. The physiological reactions were measured by multi-biofeed-back instrument before, during, and after cue exposure. BIS-Ⅱ questionnaire was used to collect information about their impulsive characteristic. Results After cue exposure, the self-reports scores of craving (t=11.24, P< 0.01), physiological index including heart rate((76.6±11.3) beats/min, F=19.23), skin conduct ((7.48± 4.25)μs, F=53.99), pupil size (t=11.73) had significant change in heroin addicts (P<0.01). Logistic regres-sion results showed that the scores of BIS-Ⅱ were related to cue-reduced craving (P=0.001,95% CI: 1.015～1. 065). Conclusions Exposure to drug-related cues can induces craving and physiological reactions in long term abstinence heroin addicts. High impulsive characteristic is a risk factor to induce drug-related craving. The inter-vention strategies should consider the impulsive characteristic and make a comprehensive intervention program to prevent relapse. Key words: Heroin dependence; Cue induce; Psycho-physiology indexDOI: 10.3760/cma.j.issn.1674-6554.2010.01.009

Discrimination between cocaine-associated context and cue in a modified conditioned place preference paradigm: role of the nNOS gene in cue conditioning

The conditioned place preference (CPP) paradigm entails appetitive learning and is utilized to investigate the motivational effects of drug and natural reward in rodents. However, a typical CPP design does not allow dissociation between cue- and context-dependent appetitive learning. In humans, context and cues that had been associated with drug reward can elicit conditioned response and drug craving. Therefore, we investigated (a) methods by which to discriminate between cue- and context-dependent appetitive learning, and (b) the role of the neuronal nitric oxide synthase (nNOS) gene in appetitive learning. Wild-type (WT) and nNOS knockout (KO) mice were trained by cocaine (20 mg/kg) in a discrete context paired with a light cue (a compound context-cue stimulus). In test 1, approach behaviour to either the training context or to the cue in a novel context was determined. WT mice showed robust preference for both cocaine-associated context and cue. nNOS KO mice acquired approach behaviour for the cocaine-associated context but not cue. This finding suggests that the nNOS gene is required for cue-dependent appetitive learning. On the following day (test 2), mice were tested for approach behaviour to the compound context-cue stimulus. Context but not cue exposure in test 1 reduced approach behaviour to the compound context-cue stimulus in test 2, suggesting that repeated context but not cue exposures diminished the conditioned response. Hence, this modified CPP paradigm is useful for the investigation of approach behaviour for both drug-associated context and cue, and allows further investigation of mechanisms underlying cue- and context-dependent appetitive learning.

The effect of prior experience on a prey’s current perceived risk

The prior experience of prey may influence how they assess the level of predation risk associated with an information source. Here, I present the results from a set of experiments that demonstrate how the prior experience of green frog (Rana clamitans) tadpoles can influence their risk assessment during exposure to the chemical cue of predatory larval dragonflies (Anax spp.) consuming conspecific tadpoles. At the short-term scale, green frog tadpoles perceived a higher level of risk when consecutive cue exposures overlapped, but only when the total chemical cue concentration was weak. Weaker chemical cue concentrations may be less reliable than stronger cue concentrations, and overlapping cue exposures may increase the degree of certainty that tadpoles have in their perceived risk. When consecutive cue exposures did not overlap, tadpoles assessed the risk associated with each cue exposure independently. Predator-conditioned tadpoles responded longer during exposure to the Anax chemical cue than nonconditioned tadpoles, which suggests that a tadpole's long-term experience eventually does influence its risk assessment. In general, the results suggest that a prey's prior experience may influence its current perceived risk by influencing either the degree of certainty in or the level of its perceived risk. Understanding how the prior experience of prey influences their current risk assessment requires that the rate of decay of the value of prior experience should be identified at two timescales as an indicator of the current level of predation risk.

The dynamics of predation risk assessment: responses of anuran larvae to chemical cues of predators

1. While the antipredator behaviour of prey has been well studied, little is known about the rules governing the predation risk assessment of prey. In this study, I measured the activity levels of predator-naive green frog (Rana clamitans) tadpoles during and after exposures to the chemical cue of predatory larval dragonflies (Anax spp.). I then used the lengths of the time lags from the end of the cue exposures until the tadpoles returned to a control level of activity as an index of the perceived risk of the tadpoles. 2. While tadpoles always responded upon exposure to the Anax chemical cue by strongly reducing their activity level, their perceived risk increased asymptotically over time during the initial period of the cue exposure. Tadpoles of all size classes perceived increasing risk in proportion to chemical cue concentration, but the length of time that tadpoles responded during cue exposure and the length of their post-exposure time lags decreased with increasing body mass. 3. The results suggest that the perceived risk of green frog tadpoles varies over time and does not correspond directly to their behavioural response (i.e. activity level). However, their perceived risk does appear to vary in accordance with the predation risk associated with the Anax chemical cue and the reliability of the information from the cue, and therefore may be predictable.

Impaired detection of chemical alarm cues by juvenile wild Atlantic salmon (Salmo salar) in a weakly acidic environment

Many prey fishes rely on damage-released chemical alarm cues to detect and avoid predators. The ability to use these cues has been shown to confer considerable survival benefits to individuals. While several laboratory studies and a single field study have demonstrated that an ambient pH of 6.0 impairs fishes in their ability to detect these alarm cues, no study had yet compared the response to alarm cue exposures across populations residing in multiple streams of a different acidity level. In our study, we conducted live behavioural observations in five nursery streams, ranging in pH from 5.71 to 7.49 on two age classes (young of the year and parr) of wild juvenile Atlantic salmon (Salmo salar). We aimed to assess if the detection of these chemical alarm cues was constantly dependant on the ambient pH or if variations in the detection occurred among populations of the different streams regardless of the ambient acidity level. Our results demonstrated that salmon present in any acidic stream did not respond to alarm cues, while those in neutral streams exhibited typical alarm responses.

Predictors of Opiate Drug Abuse during a 90-Day Methadone Detoxification

The behavioral circumstances related to opiate drug use were examined during a 90-day out-patient methadone detoxification. Seventy-one subjects (55 male and 16 female) were followed from the day of intake to treatment termination. Data were collected by means of a weekly structured interview. Questions were asked about each occasion of opiate use in the previous week with respect to time, source, cost, social circumstance, etc. Monitored urine samples were tested x 3/week to verify verbal reports. The study demonstrated beneficial effects of the detoxification treatment by showing dramatic decreases in rates and amounts of opiate drug use during treatment. The study also identified race (p less than .0008; t = -3.522; beta = -0.366), gender (p less than .0243; t = 2.305; beta = 0.222), and the number of opiate use episodes/week at baseline (p less than .0013; t = -3.364; beta = -0.338) as significant and independent predictors of treatment outcome. Current duration of regular and continuous opiate use was also found to be marginally significant. The overall regression was highly significant (p less than .0001; F = 9.176; df = 4,66). A second regression analysis with race, age, and gender excluded as independent variables was conducted in order to derive indices which were related to behavioral and environmental characteristics versus global physical/cultural identification. With race and gender removed, the overall regression was still highly significant, although less than a fifth of the variance was accounted for. The number of opiate use episodes/week at baseline and the total number of drug-related stimulus cue exposures at baseline were found to be independently significant variables in the analysis. Knowledge of the impact of such behavioral factors on the treatment process may enable us to better understand the role of environmental contributors to opiate use. Such information may also help us to direct our limited resources and to better focus our treatment interventions.