Murray E. Jarvik

Smoking withdrawal symptoms in two weeks of abstinence.

In order to study trends in smoking withdrawal symptoms, 35 participants in a smoking cessation clinic completed four questionnaires daily for 2 weeks. The questionnaire dealt with a variety of symptoms which a factor analysis showed could be grouped into four factors: stimulation, desire to smoke, and physical and psychological symptoms. Changes were observed in reports of symptoms over days. Trend analyses found that each symptom group except stimulation showed significant patterns or changes as a function of days in abstinence. These symptom clusters were all found to have U-shaped functions. In addition, desire to smoke and psychological symptoms showed linear decreases as abstinence proceeded. Light and heavy smokers were found to differ in the pattern of reported stimulation.Ss who were totally abstinent reported less severe craving overall for cigarettes than those who only reduced their cigarette consumption by an average of 60%. Also, the craving of totally abstinentSs dropped off more sharply as abstinence proceeded. The import of these patterns and trends in withdrawal symptoms as a function of time is discussed.

Differences between smokers and nonsmokers in regional gray matter volumes and densities

BACKGROUND Magnetic resonance imaging (MRI) studies have demonstrated large-scale brain abnormalities in cigarette smokers, such as ventricular enlargement and atrophy. Converging lines of evidence point to functional differences between smokers and nonsmokers in specific brain regions, namely the lateral prefrontal cortex (PFC), anterior cingulate cortex (ACC), ventral striatum, and thalamus. Using MRI, we examined these regions for differences in gray matter between smokers and nonsmokers. METHODS Thirty-six otherwise healthy adults (19 smokers and 17 nonsmoking control subjects) underwent three-dimensional Fourier-transform spoiled-gradient-recalled acquisition MRI of the brain. Both hand-drawn regions of interest and the computer program voxel-based morphometry were used to assess group differences in regional gray matter volumes and densities, respectively. RESULTS Smokers had smaller gray matter volumes and lower gray matter densities than nonsmokers in the PFC bilaterally, along with smaller volumes in the left dorsal ACC and lower gray matter densities in the right cerebellum. Smokers also had negative associations between pack-year smoking history and PFC gray matter densities. CONCLUSIONS Smokers and nonsmokers differed in regional gray matter in brain areas previously linked with nicotine dependence. These findings might reflect effects of chronic smoking, predisposing traits that lead to smoking, or some combination of these factors.

Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers

Results of this study indicate that nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Previous studies have not addressed the question of whether the stimulus for smoking-related hormone release is the ‘stress’ of smoking or a pharmacologic action of nicotine and other tobacco substrates. Nicotine exposure is controlled in this study by allowing each subject to smoke only two 2.0 mg nicotine cigarettes during one experimental session and two 0.2 mg nicotine cigarettes in another session. Plasma levels of cortisol, growth hormone, and prolactin for the higher nicotine session were found to be significantly elevated over those for the low-nicotine session, indicating that nicotine itself plays a predominate role in smoking-induced hormone increases. All hormone levels for the 2.0 mg nicotine session had not returned to baseline 60 min after smoking.

Memory facilitating and anti-amnesic effects of corticosteroids

Abstract The effects of corticosterone, hydrocortisone and dexamethasone on retention of active and passive avoidance training were studied in male mice. Posttraining administration of any of the hormones facilitated subsequent retention test performance of poorly trained mice when tested one week after training and drug administration. The optimum dose of dexamethasone was 4 mg/kg, while corticosterone and hydrocortisone were effective at 30 and 40 mg/kg, respectively. Dexamethasone significantly facilitated retention when administered up to 150 min but not at 210 min after training. It was further determined that dexamethasone blocked the amnesic effect of two but not four successive injections of anisomycin in both active and passive avoidance tasks. Corticosterone and dexamethasone when administered to anisomycin-injected mice caused only a small, transient increase in the protein synthesis inhibition. In saline-injected control mice, the hormones also caused a small inhibition of protein synthesis which disappeared quickly. Plasma corticosterone levels were measured in mice trained and given anisomycin, cycloheximide or saline. Plasma corticosterone levels were reduced 43% by anisomycin and 89% by cycloheximide. In both cases the corticosterone levels subsequently increased rapidly after the inhibitor injection and were elevated by about 5 times above control levels at 130 min after the inhibitor injection. The results are discussed in terms of the effect of central stimulant action of corticosteroids on memory formation.

Nicotine abstinence produces content-specific stroop interference

Adult, male smokers were randomly assigned to be nicotine abstinent for 12 h (n=10) or to smoke normally for the same period of time (n=10). Performance on a modified version of the Stroop (1935) color-naming task, where subjects named the color of ink in which each of a series of words was written, showed that abstinent smokers took significantly longer to color-name words related to cigarette smoking (e.g., Lighter) than to color-name neutral control words (e.g., Pennant). Non-abstinent smokers showed a significant difference in the opposite direction. These results suggest that nicotine abstinence decreases the ability to ignore the meaning of smoking-related information. This finding supports the hypothesis that abstinence produces a content-specific shift in attentional focus. The present pattern of results cannot be explained by a general decrease in cognitive function due to nicotine abstinence.

Cholinergic receptor interactions and their effects on long-term memory processing

Mice were treated on active avoidance to determine the effect of cholinergic and anticholinergic drugs on retention. All drugs were administered intraventricularly after training and one week prior to testing retention. A dose-response curve was determined for each drug. The results indicate that each of 6 anticholinergics impaired retention. The 8 cholinergic drugs tested all yielded U-shaped dose-response curves with controls showing poor retention, low doses of the drugs yielding good retention and high doses resulting in poor retention.

Cigarette smoking during anxiety-provoking and monotonous tasks☆

Cigarette smokers were exposed to three conditions within a single session: stagefright anxiety, monotonous concentration, and a relaxation control. One cigarette was lit during the second 10-minute half of each condition, and smoking topography (number of puffs and cumulative volume smoked) was continuously recorded. Subjects smoked significantly more in the two task conditions than during relaxation, supporting the hypothesis that anxiety-provoking and attention-demanding situations elicit smoking. Younger subjects increased their smoking more than older subjects during stagefright , and females responded more than males to the concentration task.

Pain inhibition, nicotine, and gender

The ability of nicotine to decrease sensitivity to pain in humans has been a subject of dispute. Decreased sensitivity has been demonstrated in studies involving men, whereas the effect has been less obvious or absent in studies involving predominantly, or entirely, women. To determine whether there are gender differences in nicotines hypoalgesic actions, ratings of electrocutaneous stimulation were obtained from 30 male and 44 female smokers and nonsmokers under placebo and nicotine conditions. Nicotine increased the pain threshold and tolerance ratings of men but had no effect on the pain ratings of women. Among men, there was no effect of smoking history, suggesting that the changes in pain perception reflect a direct pain-inhibitory effect of nicotine rather than a relief from acute nicotine withdrawal. Nicotine had no effect on mood or task ratings, indicating that the antinociceptive effects observed were not due to nicotines putative mood effects.

Chronic nicotine and withdrawal effects on radial-arm maze performance in rats

Rats were tested for choice accuracy in an eight-arm radial maze during and after chronic administration of nicotine via subcutaneously implanted glass and Silastic capsules. Nicotine administration significantly improved choice accuracy relative to controls. The effect gradually became apparent over the first 2 weeks of exposure and persisted through the third week. Surprisingly, the significant facilitation of the nicotine-treated rats relative to controls continued for 2 weeks after the end of nicotine administration. No effects of nicotine were seen on choice latency or the strategy to make adjacent arm entries.

Nicotine tolerance in rats; role of dose and dose interval

In experimentally naive rats, nicotine reduced spontaneous locomotor activity in a dose-related manner. After a single pretreatment with nicotine, acute tolerance developed; this was shown by a shift of the dose-response curve, such that the dose of nicotine required to produce a given decrement in activity was multiplied by a factor of about 2.4. In a second experiment, a range of doses of nicotine was found to induce tolerance, but the dose inducing the maximum degree of tolerance was rather critical. The results demonstrated the importance of using a range of pretreatment and challenge doses when assessing tolerance to nicotine. However, frequently repeated doses were not necessary, since tolerance developed when nicotine was administered to rats only once in every 3 days. In terms of tolerance liability in rats, it seems that nicotine is not discriminable from other drugs upon which dependence can be established.