The effects of psychological stress on approach tendencies for smoking-related cues in smokers.

Stress may potentiate the chronification of nicotine addiction, but the exact mechanisms remain elusive. We performed an explorative pilot study examining the effects of psychological stress, administered via the socially evaluated cold pressor task (SECPT), on implicit approach bias for smoking-related cues in smokers in the approach-avoidance task (AAT). Smokers (N = 24) were subjected to the stress or control condition of the SECPT by using a within-subject design. Consistent with previous findings, a strong approach bias for smoking-related cues in the AAT was found in smokers. Exposure to stress did not affect the general bias for smoking-related cues in the AAT relative to the control condition of the SECPT. In additional explorative analyses, an interaction among carbon monoxide (CO) levels in expired air, cortisol levels, and stress on approach bias for smoking-related cues was found. Higher CO levels, possibly due to recent smoking, prior to stress exposure were associated with an approach bias for smoking-related cues. Our results suggest that CO levels in interaction with stress can modulate implicit, automatic processing in the context of nicotine addiction. Our findings might provide novel cues to how stress influences cigarette craving and smoking behavior.

The dopamine D2 receptor mediates approach-avoidance tendencies in smokers.

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. Using the approach-avoidance task (AAT), we recently demonstrated that smokers show an increased approach-bias toward smoking-related cues but not toward naturally rewarding stimuli. Here, we examined the contribution of the DRD2 Taq1B polymorphism to smokers' and non-smokers' responsivity toward smoking versus naturally rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. In addition, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e., AAT modification paradigms, in smokers.

Generalization of Extinguished Fear to Untreated Fear Stimuli after Exposure.

Exposure therapy is highly effective in treating excessive fear related to specific objects and/or situations. However, patients with anxiety disorders often display a generalization of fear responses toward conceptually and perceptually related stimuli and situations. It is unclear whether the beneficial effects of exposure on fear reduction toward treated fear stimuli can extend to untreated fear stimuli. Here, we investigated whether basic principles of extinction generalization apply to exposure. Spider-phobic participants were randomly assigned to either two sessions of exposure treatment (n=23) with spiders or no-treatment (n=24). Prior to and after treatment, behavioral approach tests (BATs) were conducted to examine avoidance, fear and disgust responses toward the treated phobic stimulus (spider as the extinction stimulus). Likewise, BATs with the untreated fear stimulus (cockroach) were conducted to dissect the generalization of treatment effects. Treatment was highly effective in increasing approach behavior toward both treated and untreated fear stimuli. Generalization of treatment effects were evident on the behavioral (approach distance during the BAT), subjective (fear levels during the BAT) and psychophysiological level (heart rate during the BAT). However, a stronger decline in disgust was only evident for the treated fear stimulus. Notably, the herein attained generalization effects were not context-dependent. Hence, exposure therapy for spider phobia was effective in reducing fear of untreated stimuli which share common fear-evoking characteristics with spiders but were never presented during the respective exposure treatment. These findings provide clinical evidence for extinction generalization across different fear-evoking stimuli mediated via exposure.

Approach bias modification in inpatient psychiatric smokers.

Drug-related automatic approach tendencies contribute to the development and maintenance of addictive behavior. The present study investigated whether a nicotine-related approach bias can be modified in smokers undergoing inpatient psychiatric treatment by using a novel training variant of the nicotine Approach-Avoidance-Task (AAT). Additionally, we assessed whether the AAT-training would affect smoking behavior. Inpatient smokers were randomly assigned to either an AAT-training or a sham-training condition. In the AAT-training condition, smokers were indirectly instructed to make avoidance movements in response to nicotine-related pictures and to make approach movements in response to tooth-cleaning pictures. In the sham-training condition, no contingency between picture content und arm movements existed. Trainings were administered in four sessions, accompanied by a brief smoking-cessation intervention. Smoking-related self-report measures and automatic approach biases toward smoking cues were measured before and after training. Three months after training, daily nicotine consumption was obtained. A total of 205 participants were recruited, and data from 139 participants were considered in the final analysis. Prior to the trainings, smokers in both conditions exhibited a stronger approach bias for nicotine-related pictures than for tooth-cleaning pictures. After both trainings, this difference was no longer evident. Although reduced smoking behavior at posttest was observed after both trainings, only the AAT-training led to a larger reduction of nicotine consumption at a three-month follow-up. Our preliminary data partially support the conclusion that the AAT might be a feasible tool to reduce smoking in the long-term in psychiatric patients, albeit its effect on other smoking-related measures remains to be explored.

"A cigarette a day keeps the goodies away": smokers show automatic approach tendencies for smoking--but not for food-related stimuli.

Smoking leads to the development of automatic tendencies that promote approach behavior toward smoking-related stimuli which in turn may maintain addictive behavior. The present study examined whether automatic approach tendencies toward smoking-related stimuli can be measured by using an adapted version of the Approach-Avoidance Task (AAT). Given that progression of addictive behavior has been associated with a decreased reactivity of the brain reward system for stimuli signaling natural rewards, we also used the AAT to measure approach behavior toward natural rewarding stimuli in smokers. During the AAT, 92 smokers and 51 non-smokers viewed smoking-related vs. non-smoking-related pictures and pictures of natural rewards (i.e. highly palatable food) vs. neutral pictures. They were instructed to ignore image content and to respond to picture orientation by either pulling or pushing a joystick. Within-group comparisons revealed that smokers showed an automatic approach bias exclusively for smoking-related pictures. Contrary to our expectations, there was no difference in smokers' and non-smokers' approach bias for nicotine-related stimuli, indicating that non-smokers also showed approach tendencies for this picture category. Yet, in contrast to non-smokers, smokers did not show an approach bias for food-related pictures. Moreover, self-reported smoking attitude could not predict approach-avoidance behavior toward nicotine-related pictures in smokers or non-smokers. Our findings indicate that the AAT is suited for measuring smoking-related approach tendencies in smokers. Furthermore, we provide evidence for a diminished approach tendency toward food-related stimuli in smokers, suggesting a decreased sensitivity to natural rewards in the course of nicotine addiction. Our results indicate that in contrast to similar studies conducted in alcohol, cannabis and heroin users, the AAT might only be partially suited for measuring smoking-related approach tendencies in smokers. Nevertheless, our findings are of special importance for current etiological models and smoking cessation programs aimed at modifying nicotine-related approach tendencies in the context of a nicotine addiction.

Superior working memory and behavioural habituation but diminished psychomotor coordination in mice lacking the ecto-5'-nucleotidase (CD73) gene.

Adenosine is an important neuromodulator in the central nervous system involved in the regulation of wakefulness, sleep, learning and memory, fear and anxiety as well as motor functions. Extracellular adenosine is synthesized by the cell-surface ectoenzyme ecto-5'-nucleotidase (CD73) from 5'-adenosine monophosphate. While CD73 is widely expressed throughout the mammalian brain, its specific role for behaviour is poorly understood. We examined spatial working memory, emotional responses, motor coordination and motor learning as well as behavioural habituation in mice with a targeted deletion of CD73. CD73 knockout (CD73-/-) mice exhibit enhanced spatial working memory in the Y-maze and enhanced long-term behavioural habituation in the open field. Furthermore, impaired psychomotor coordination on the accelerating rotarod was found in CD73-/- mice. No changes in motor learning and/or anxiety-like behaviour were evident in CD73-/- mice. Our data provide evidence for a role of CD73 in the regulation of learning and memory and psychomotor coordination. Our results might be important for the evaluation of adenosine neuromodulators as possible treatments to ameliorate cognitive and motor deficits associated with neurodegenerative diseases.