Personality related effects of nicotine, mode of application, and expectancies on performance, emotional states, and desire for smoking.

Three separate factors relevant to nicotine effects have been investigated in this experiment in combination: the experimentally induced expectation about receiving a sham or a nicotine cigarette, the mode of application of nicotine by a tablet, by a cigarette or not at all, while the belief of receiving the nicotine via smoking was held constant in each condition (by nicotine or sham smoking), and the personality factors of extraversion or neuroticism, respectively. Ninety-six healthy female student smokers were tested in a 2 x 3 x 2 factorial group comparison design with respect to critical flicker fusion and reaction time performance as well as to self-ratings on emotional and cortical arousal and ratings on desire for further cigarettes (satisfaction from smoking a single cigarette containing either 0.8 mg nicotine or a sham cigarette). In each case, a tablet containing either nicotine or placebo was administered together with the cigarette. The results showed that performance is sensitive to interaction effects of instruction and mode of application. The instruction of sham or nicotine assignment when applied with a congruent treatment (sham with a sham cigarette, or nicotine with a nicotine cigarette) both increased performance, while groups with discordant information showed worse performance. The administration of nicotine by tablets or by smoking differs considerably, nicotine cigarettes causing a stronger increase in emotional arousal, tablets rather a decrease or no effect, while the true placebo condition increases arousal due to deprivation effects. This leads to an enhancement of the nicotine effect with real smoking and to reactive increase of effort when sham smoking. The instruction affects alertness, the nicotine illusion leading to a lower reduction in subjective reports of alertness and concentration than that observed with the sham instruction. Neurotic subjects become more anxious and tense with nicotine cigarettes than stable subjects. This effect is less pronounced or even reversed with tablets. No interactions with instructions are observed with neuroticism. Extraverts tend to show a decrease in performance but an increase in alertness with the instruction of receiving nicotine as opposed to the sham expectation, whereas introverts behave the opposite way. Subjective ratings on arousal seem to follow the law of transmarginal inhibition, with extraverts being pushed from low arousal to high and introverts vice versa by the mere expectation.

[Explanatory models of anxiety from the viewpoint of biopsychology and pharmacopsychology]. / Erklärungsmodelle der Angst aus der Sicht der Biopsychologie und Pharmakopsychologie.

To understand the biological basis of anxiety, the following psychological aspects are discussed: The difference between "trait" and "state" anxiety, types of anxiety as related to knowledge about causes and consequences, anxiety as a chronological process involving coping strategies and different levels of responses. The lack of specificity is physiological indicators of anxiety is demonstrated by experiments based on electrodermal and cardiovascular responses. Among hormones, special emphasis is placed on the constellation between catecholamines and cortisol as being relevant for anxiety research. It is emphasized that configurations of hormone parameters may be more relevant predictors for anxiety than single response values, and the study of postoperative catecholamine and cortisol responses is used for demonstrating differences between patients in a high and low preoperative state of anxiety. Differences are observed only on the emotional and pain response levels, but not in physiological parameters. The neurophysiological model representing central nervous system substrates for anxiety is the behavioural inhibitory system described in the theory by Gray [17], and the most relevant transmitters noradrenaline, serotonin, and the GABA-system are discussed with regard to their relevance for anxiety in animal studies, in studies using provocation tests with pharmacological substances, and in clinical studies with anti-anxiety drugs. Experimental anxiety research in psychology is frequently characterised by significant interactions between many mediators of responses, in particular the type of stressor, the level of trait anxiety and other personality variables, and the type of substances used. It is concluded that stressors as well as drugs frequently do not specifically induce anxiety but may nonspecifically affect general arousal and may only be operating in certain groups and certain levels of stress intensity.

The antagonism of ipsapirone induced biobehavioral responses by +/- pindolol in high and low impulsives.

The present study was conducted to investigate whether +/- pindolol antagonizes ipsapirone induced biobehavioral changes in a personality dependent way. Our previous work demonstrated that high impulsives show higher immune cell responses than low impulsive subjects upon treatment with ipsapirone. A total number of 80 healthy male volunteers received placebo (N = 20) or 10 mg ipsapirone (N = 20), 30 mg +/- pindolol (N = 20), or a combination of 30 mg +/- pindolol and 10 mg ipsapirone (N = 20). Each group consisted of 10 low and 10 high impulsive subjects. Since 5-HT related drugs induce thermoregulatory responses, the study took place in a climate chamber with a constant ambient temperature. Blood samples (for measurement of CD4+ cell counts) were drawn from an indwelling catheter invisibly for the subjects. The results clearly demonstrate that the ipsapirone induced decreases in body temperature and number of peripheral CD4+ cells are more pronounced in high impulsives. +/- Pindolol antagonizes thermoregulatory and CD4+ cell responses. The results are discussed with respect to mechanisms of alteration in 5-HT function related to impulsivity.

Personality correlates of +/- pindolol induced decreases in prolactin.

The present study was conducted to investigate if personality traits can be usefully related to serotonergic vs. dopaminergic action of the 5-HT1a-antagonist +/- pindolol. Forty healthy male volunteers (aged between 20 and 30 years) were randomly assigned to a placebo or a +/- pindolol (30 mg, oral dose) group in a double blind trial. Blood samples were drawn and analyzed for PRL concentrations. In addition, the subjects completed questionnaires on personality. The results indicated that +/- pindolol decreases PRL concentrations depending on personality. While subjects high on impulsivity and related traits (aggression and disinhibition) show lower PRL decreases, well-being and personality traits frequently related to dopaminergic activity were not correlated with changes in PRL. Since reduced (blunted) PRL-responses after 5-HT challenge tests have been reported for impulsives, the present results favor the involvement of primarily serotonergic and probably only secondarily dopaminergic control of +/- pindolol induced PRL decreases.

Changes in cortisol secretion during shiftwork: implications for tolerance to shiftwork?

The present study was conducted to determine the size of changes and the time point of those changes in biological rhythms during night-shift and whether they are associated with tolerance to shiftwork. The adrenal hormone cortisol has frequently been investigated in the field of shiftwork since it follows a pronounced circadian variation and has been demonstrated to be affected by night-work. However, studies are restricted with respect to sample size, number of measurements or duration of sampling periods. Therefore, a sample of 24 night-shift workers was investigated in a cardiac emergency unit for seven nights. Saliva samples were collected frequently for determination of cortisol. A total of 28 cortisol measurements in each subject were made in order to decide whether the circadian rhythm changed, and if so at which time point. A clear reversal of circadian function could be observed for the total group (mean cortisol concentrations) after the fifth night. However, inspection of individual patterns revealed that six out of 24 subjects did not change in circadian function. These subjects exhibited lower durations of and less consistency in recovery sleep across the following days after night-work. With respect to personality dimensions a pattern associated with neuroticism can be observed in subjects without appropriate changes in cortisol rhythm. However, owing to the small sample size of non-adapters these results are preliminary and should be replicated with larger samples. The overall relationship between neuroticism and low adaptability has been discussed.

Mechanisms of phospholipase D stimulation by m3 muscarinic acetylcholine receptors. Evidence for involvement of tyrosine phosphorylation.

In human embryonic kidney cells stably expressing the human m3 muscarinic acetylcholine receptor (mAChR) subtype, agonist (carbachol) activation stimulated phospholipase C, increased cytoplasmic calcium concentration, induced tyrosine phosphorylation of various cellular proteins and activated phospholipase D. Bypassing membrane receptors, phospholipase D was activated in these cells by direct activation of protein kinase C by phorbol esters, by direct activation of GTP-binding proteins by A1F4- and a stable GTP analogue (in permeabilized cells), by increasing cytoplasmic calcium concentration with the calcium ionophore A23187 and also apparently by tyrosine phosphorylation. In order to identify possible mechanisms by which the m3 mAChR couples to phospholipase D, various inhibitors of protein kinase C, tyrosine kinases and calcium-dependent events were studied. Prevention of an agonist-induced increase in cytoplasmic calcium concentration did not alter the mAChR-induced phospholipase D stimulation. The protein kinase C inhibitors, calphostin C and staurosporine, efficiently prevented phospholipase D activation by phorbol 12-myristate 13-acetate but only partially inhibited the activation induced by the mAChR agonist. Additionally, down-regulation of protein kinase C by prolonged exposure to phorbol 12-myristate 13-acetate abrogated phospholipase D activation by this effector but had only minor or no effects on the response to the mAChR agonist and direct activators of GTP-binding proteins. In contrast, the tyrosine kinase inhibitor genistein abolished the carbachol-induced and A1F4(-)-induced phospholipase D activation but had no effect on enzyme activation by phorbol 12-myristate 13-acetate. The data indicate that phospholipase D in m3 mAChR-expressing human embryonic kidney cells can be activated by various different mechanisms, i.e. receptor agonists, GTP-binding proteins, protein kinase C-dependent and calcium-dependent events and tyrosine phosphorylation. The coupling of m3 mAChR to phospholipase D appears to be largely independent of concomitant phospholipase C activation with subsequent increase in cytoplasmic calcium concentration and protein kinase C activity. The data instead suggest the involvement of an essential protein tyrosine phosphorylation mechanism in phopsholipase D activation by the m3 mAChR and heterotrimeric GTP-binding proteins.