Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance.

Effects of nicotine and caffeine, separately and in combination, were assessed in 12 male habitual smokers in a repeated-measures design. Caffeine (0-mg vs. two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs. 1.0-mg machine-delivered dose vs. 0.05-mg machine-delivered dose). Participants smoked a total of five cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on electroencephalogram (EEG) power; however, these effects were modulated by the eyes open versus closed condition, the other drug, and electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs.

EEG, physiology, and task-related mood fail to resolve across 31 days of smoking abstinence: relations to depressive traits, nicotine exposure, and dependence.

Changes in task-related mood and physiology associated with 31 days of smoking abstinence were assessed in smokers, 34 of whom were randomly assigned to a quit group and 22 to a continuing-to-smoke control group. A large financial incentive for smoking abstinence resulted in very low participant attrition. Individuals were tested during prequit baselines and at 3, 10, 17, and 31 days of abstinence. Abstinence was associated with decreases in heart rate and serum cortisol, a slowing of electroencephalogram (EEG) activity, and task-dependent and trait-depression-dependent hemispheric EEG asymmetries. Differences between the quit group and the smoking group showed no tendency to resolve across the 31 days of abstinence. Trait depression and neuroticism correlated with increases in left-relative-to-right frontal EEG slow-wave (low alpha) activity at both 3 and 31 days of abstinence. In contrast, prequit nicotine intake and Fagerström Tolerance scores correlated with alpha asymmetry and with greater EEG slowing only at Day 3. Thus, the effects of smoking abstinence appear to last for at least several months.

Effects of monetary contingencies on smoking relapse: influences of trait depression, personality, and habitual nicotine intake.

Of 56 male smokers, 34 were randomly assigned (by 60% random odds) to quit smoking immediately, whereas the remaining 22 were assigned to quit after an additional 31 days. Compensation ($300) was contingent on abstinence for a minimum of 31 or 2 days (depending on random assignment) and completion of all experimental sessions. Contingencies for the immediate-quit group required 31 days of abstinence; those for the delayed-quit group required only 2 days of abstinence. Contingency duration (31 vs. 2 days) predicted days to relapse. All but 4 of the 31-day contingency participants maintained abstinence for at least 31 days, whereas only 3 of the 2-day contingency group abstained for 31+ days. However, 31-day contingencies did not result in longer postcontingency time to relapse. Higher trait neuroticism, depression, and psychopathic deviate scores predicted decreased time to relapse. Prequit cotinine concentrations and Fagerström Tolerance Questionnaire scores failed to predict time to relapse.

Cardiovascular and mood responses to quantified doses of cigarette smoke in oral contraceptive users and nonusers.

Previous research suggests that the female sex hormones may moderate cardiovascular and mood responses to cigarette smoking and abstinence. To test this possibility, acute effects of cigarette smoking on cardiovascular reactivity and mood were examined in 12 oral contraceptive users and 12 nonusers across two menstrual phases (early and late cycle). After overnight deprivation, each participant attended two sessions in which they first sham-smoked and then smoked two standard cigarettes, via a quantified smoke delivery system. Oral contraceptive users exhibited larger cigarette smoking-induced increases in heart rate compared with nonusers. In addition, cigarette smoking-induced cardiovascular changes varied with both the phase of the menstrual cycle and oral contraceptive use. No menstrual phase-dependent effects were observed for tobacco withdrawal symptoms, premenstrual symptoms, or moods prior to smoking. Cardiovascular hyperreactivity to cigarette smoke in oral contraceptive users may help explain the mechanisms by which smoking and oral contraceptive use contribute to an elevated risk for coronary heart disease.

Structure and chromosomal localization of mouse G protein subunit gamma 4 gene.

The G protein gamma subunits are members of a multigene family and are implicated in determining the specificity of receptor-G protein interaction. The gene structures for many of the gamma subunits remain to be determined. Here, we report the gene structure for the brain-specific gamma 4 subunit and its map position on a mouse chromosome. The gene (Gng4) comprises at least three exons spanning over 20 kb. The 225-bp coding region, which spans two exons, is interrupted by a large 18.2-kb intron whose position is conserved in other gamma subunit genes. There is a putative additional intron in the 5' untranslated region just upstream of the translation initiation codon. Introns are present in most of the other gamma subunits at this position. The mouse Gng4 gene is mapped to chromosome 13.

Noise stress does not modulate effects of smoking/nicotine on beta-endorphin, cortisol, ACTH, glucose, and mood.

Noise-dependent effects of smoking multiple cigarettes on subjective state and blood concentrations of ACTH, beta-endorphin, cortisol, and glucose were assessed in a repeated measures design where noise level (high versus minimal) was crossed with nicotine dose (quasi-ad lib own brand versus 1.0 mg FTC nicotine machine-delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Cortisol and ACTH were increased by nicotine, but not by noise and there was no noise by dose interaction. In contrast, nicotine did not increase beta-endorphin in either noise condition and there was no dose by noise interaction for beta-endorphin. However, noise was associated with a modest increase in beta-endorphin. The effects of nicotine on blood glucose varied as a function of the number of cigarettes smoked. However, the effects of nicotine on glucose, hormones, and subjective state did not vary as a function of noise stress.

Does noise stress modulate effects of smoking/nicotine? Mood, vigilance, and EEG responses.

Effects of smoking multiple cigarettes on EEG, vigilance, and subjective state were assessed in a repeated measures design where noise level (high versus minimal) was crossed with nicotine dose (quasi-ad lib own versus 1.0 mg FTC nicotine machine-delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Vigilance was increased by nicotine, but not by noise and there was no noise by dose interaction. Effects of nicotine on EEG varied as a function of dose, noise, hemisphere, time, and eyes-open versus eyes-closed condition. Smoking normal nicotine delivery (0.9-1.1 mg FTC-estimated) cigarettes resulted in decreases in percentages of delta and theta EEG magnitude and increased percentage beta-1 EEG magnitude across conditions and time. Changes in alpha and theta magnitude were dependent on eyes being open versus closed. Hemispheric asymmetries varied as a function of noise and time. Consistent with inverted "U" models, effects of nicotine on EEG were clearly stimulant during the quiet conditions while there were minimal to no differences between nicotine doses during the high-noise conditions. The failure of nicotine to modify mood is interpreted in terms of bioinformational models of nicotine's subjective effects.

Increased regional cerebral glucose metabolism and semantic memory performance in Alzheimer's disease: a pilot double blind transdermal nicotine positron emission tomography study.

Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.

Yeast communities associated with Drosophila species and related flies in an eastern oak-pine forest: a comparison with western communities.

Intestinal yeast mycobiota were studied in 14 species of Drosophila and in the drosophilid species Chymomyza amoena, captured at Pinery Provincial Park, Ontario. Over 56 yeast species, some undescribed, were isolated. These yeast communities were compared with those from two similar surveys conducted in western portions of North America. The community structures were influenced significantly by the habitat rather than phylogeny of the flies. Geographic separation was a factor affecting yeast taxa frequencies in the fly species, but it was largely overshadowed by ecological factors when the communities were described physiologically. The notion that habitats are filled by yeasts which add up to a suitable physiological potential, more or less independently of their taxonomic affinities, was thus confirmed.

Immune function in cigarette smokers who quit smoking for 31 days.

A group of 28 healthy, white, male, light-to-moderate smokers, 21 to 35 years of age, were offered a financial inducement to abstain from smoking for 31 days. A matched control group of 11 smokers were paid to continue smoking during the same period. Nonspecific parameters of immune system function were monitored before and at various times after smoking abstinence. Abstinence increased natural killer cell cytotoxic activity but did not alter mitogen-induced T-lymphocyte proliferation as measured by responses to concanavalin A or phytohemagglutinin. Serum cortisol concentrations also decreased after smoking cessation; however, changes in immune function were not correlated with serum cortisol change, nor with indices of smoking such as plasma nicotine and cotinine levels. Responses to concanavalin A and phytohemagglutinin were positively correlated with change in self-reported alcohol ingestion during smoking abstinence. Results indicate that elevation in natural kill cell cytotoxic activity is detectable within 1 month of smoking cessation, even in light-to-moderate smokers. However, elevation in natural killer cell cytotoxic activity appears not to be directly related to cessation-induced reductions in plasma nicotine, cotinine, or circulating cortisol levels.

Personality, psychopathology, and nicotine response as mediators of the genetics of smoking.

Individual differences in psychopathology, personality, and nicotine responsivity and their biological bases are evaluated as mechanisms potentially mediating smoking heritability. Smokers are more likely to be high in neurotic traits (e.g., depression, anxiety, anger) and in social alienation (psychoticism, impulsivity, unsocialized sensation-seeking, low conscientiousness, low agreeableness) and low in achievement/socioeconomic status. Psychological and biological mechanisms putatively mediating these associations are reviewed. It is concluded that a number of relatively indirect and complex processes, as well as more direct (e.g., self-medication for psychopathology, nicotine sensitivity), mediate the inheritance of smoking behavior.

The Ribonuclease P database.

The Ribonuclease P Sequence database is a compilation of RNase P sequences, sequence alignments, secondary structures, three-dimensional models, and accessory information. In its initial form, the database contains information on RNase P RNA in bacteria and archaea, and RNase P protein in bacteria. The sequences themselves are presented phylogenetically ordered and aligned. The database also contains secondary structures of bacterial and archaeal RNAs, including specially annotated 'reference' secondary structures of Escherichia coli and Bacillus subtilis RNase P RNAs, a minimum phylogenetic consensus structure, and coordinates for models of three-dimensional structure.

Flexible effects of quantified cigarette-smoke delivery on EEG dimensional complexity.

A quantified smoke delivery system (QSDS) was used to experimentally control the administration of inhaled cigarette smoke to 28 male smokers. One puff (2 s, 35 cc) was taken every 30 s on a cigarette (nicotine yield 1.0 mg) until the char line reached 3 mm from the filter wrap. The smoke was inhaled for 5 s. Resting eyes-closed and eyes-open EEG was recorded from F3, F4, P3, and P4 before and after quantified smoke delivery (QSD). EEG dimensional complexity (DCx, a measure derived from chaos theory) was computed using the Takens-Ellner method. QSD appeared to have a 'flexible' effect on EEG DCx, primarily lowering it in subjects whose pre-smoking level was high, not affecting it in subjects whose pre-smoking level was intermediate, and tending to raise it in subjects whose pre-smoking level was low. This replicates previous results obtained with ad libitum smoking, suggesting the hypothesis that smoking may have an "optimizing" effect on the complexity of brain dynamics.

Subjective correlates of cigarette-smoking-induced elevations of peripheral beta-endorphin and cortisol.

Two experiments assessed subjective and hormonal effects of smoking cigarettes with three different nicotine deliveries. In experiment 1, 12 males smoked two cigarettes on three different occasions: (1) nicotine-free; (2) their own brand (1.0 mg FTC-estimated nicotine delivery); or (3) 2.4 mg FTC nicotine cigarettes. In experiment 2, 12 males smoked cigarettes of comparable nicotine yield using a quantified smoke delivery system (QSDS). Blood was sampled 2 min after each cigarette completion. Relative to nicotine-free smoking, plasma beta-endorphin (BE) and serum cortisol concentrations increased after quasi-ad libitum smoking of 2.4 mg, but not after 1.0 mg nicotine cigarettes. Self-reported malaise (nausea, sickness, and unpleasantness) also increased after smoking 2.4 mg nicotine cigarettes; subjective distress was correlated with changes in blood BE and cortisol. Smoking 1.0 mg cigarettes did not increase BE or cortisol, or subjective distress. QSDS smoking produced hormonal and subjective effects similar to quasi-ad libitum smoking; however, correlations between neuromodulator concentrations and mood were non-significant. These findings suggest that the elevated levels of plasma BE and cortisol reported in some smoking studies may not be characteristic effects of normal smoking.

Hormonal and subjective effects of smoking the first five cigarettes of the day: a comparison in males and females.

The effects of smoking normal-nicotine-delivery cigarettes on serum cortisol, plasma beta-endorphin (BE), and mood were measured in 8 male and 8 female smokers; 8 male and 8 female nonsmokers served as sham-smoking controls. Smoking five cigarettes of the smokers' usual type after overnight deprivation, either ad lib or via a quantified smoke delivery system, produced small but reliable elevations in serum cortisol concentrations; BE was elevated somewhat after two, but not after four or five cigarettes. Smoking-induced elevations in serum cortisol were correlated with decreases in self-reported drowsiness after two and five cigarettes. Additionally, female smokers reported more drowsiness at baseline and after smoking nicotine-free cigarettes than did male smokers or female nonsmokers. Results suggest that smoking-induced elevations in serum cortisol, which persist for at least the first five cigarettes of the day, may modulate the arousing effects of smoking under conditions of low arousal. Also, nicotine-deprived female smokers may experience subnormal arousal compared to male smokers or female nonsmokers.

Cardiovascular responses to a quantified dose of nicotine as a function of personality and nicotine tolerance.

Correlations between cardiovascular effects of a quantified dose of nicotine and personality measures previously shown to predict coronary heart disease were obtained. Thirty male smokers smoked a popular brand of a regular strength cigarette (1.0 mg FTC-estimated nicotine delivery) on one occasion and a nicotine-free cigarette on another occasion by means of a quantified smoke delivery system. Partial correlations controlling for effects of body weight, questionnaire-assessed nicotine tolerance, and cardiovascular responses to the nicotine-free control cigarette showed Jenkins Activity Survey Type A scores to correlate positively with nicotine-induced increase in diastolic blood pressure but negatively with nicotine-induced increase in systolic blood pressure. Partial correlations indicated that trait anxiety and depression were significantly associated with nicotine-induced heart rate increases but not with nicotine-induced blood pressure responses.

Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration.

In the first experiment a conditioned taste aversion paradigm was used to characterize a dose-response curve for the aversive properties of nicotine in male Sprague-Dawley rats. Doses of nicotine ranging from 0.01 to 0.46 mg/kg, 2.0 ml of 0.47 M lithium chloride, or saline were injected, ip, 10 min after exposure to a novel saccharin solution. Amount of saccharin consumed in a two-bottle test was assessed 72 h later. Nicotine doses of 0.046 mg/kg and above produced a significant degree of conditioned taste aversion. In a second experiment, four groups of 10 rats each were injected with saline, 0.022 mg/kg nicotine, 0.46 mg/kg nicotine, or 2.0 ml 0.47 of M LiCl. Doses of 0.46 mg/kg nicotine and 0.47 M LiCl elevated plasma beta-endorphin concentrations significantly above saline control values. The 0.022 mg/kg dose, the highest dose that did not produce conditioned taste aversion in Experiment 1, did not significantly increase plasma beta-endorphin concentrations. This finding suggests that doses of nicotine that produce conditioned taste aversion also promote the release of pituitary stress hormones. Taken together these data suggest that some of the pharmacological and behavioral effects attributed to nicotine, including the release of endogenous neuromodulators, may be dose-dependent concomitants of the aversive effects of nicotine in nicotine-naive animals.

Two Hypercard calculators for molecular biology.

Two calculators built in Macintosh Hypercard are described. GelFragSizer estimates and plots DNA restriction fragment sizes, using the local reciprocal or cubic spline methods. Enzyme Kinetics estimates the Michaelis-Menton rate parameters for enzyme-catalyzed reactions, and plots data versus estimated curve in a variety of formats. These stacks help to demonstrate the ease and sophistication of calculation tools that scientists can develop with Hypercard.