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Despite being the most widely consumed psychoactive substance in the world, there is considerable confusion regarding the effects of caffeine. This study examined objective indices of performance, and self-reported mood, headache, and sleep in 36 healthy male and female habitual caffeine consumers exposed to a pattern of moderate intake. A double-blind placebo-controlled cross-over design with counterbalancing was employed in which all subjects participated in four experimental conditions involving the ingestion of placebo or caffeine 3 times daily for 6 days followed by a 7th (challenge) day of placebo or caffeine ingestion. No evidence was found that caffeine improved performance, either in the context of acute or habitual use. On the contrary, performance was found to be significantly impaired when caffeine was withdrawn abruptly following habitual use. Participants reported feeling more alert and less tired following acute ingestion of caffeine, but feeling less alert in conjunction with chronic exposure to the drug. In addition, caffeine withdrawal was associated with reported increases in frequency and severity of headache, and with reports of sleeping longer and more soundly.

The present study evaluated chronic oral treatment of rats with haloperidol or clozapine. Drugs were given in the drinking water for a 23-day period . Rat behavior was analyzed once a week in an open field. Rats ingested either 1.7 mg/kg haloperidol or 40 mg/kg clozapine daily. Blood serum analysis revealed concentrations of 6 ng/ml for haloperidol and 22 ng/ml for clozapine at the end of the treatment. Haloperidol decreased overall activity from the onset of treatment. Clozapine showed similar effects only on the last test day. Control animals showed a slight habituation in exploration-related parameters. In conclusion, these results indicate that oral drug administration through the drinking water is a suitable mode of noninvasive chronic treatment that led to sufficiently high drug levels to induce specific pharmacological effects in rats.

Memory loss and severe cognitive deficits in Alzheimer patients are supposed to be related to a reduction of acetylcholine as well as to central nervous deactivation. For the investigation of cholinergic deficits and deactivation, we used computer-assisted pupillometry. Cholinergic deficits caused by a particularly severe loss of cholinergic neurons may be responsible for cognitive and mnemonic performance deficits. The control of the pupillary diameter represents a balance between cholinergic and adrenergic innervation and is influenced directly or indirectly by central and autonomic nervous system inputs. Either of these systems could be affected in Alzheimer patients. A reduced innervation of the target muscle through neuronal cell death, axon retraction, reduced release, increased reuptake of altered amounts or function of neurotransmitter receptors seems to affect the pupillary response to cholinergic antagonists in Alzheimer patients. There is, however, no relationship between pupillary diameter and central deactivation, but between central nervous activation and pupillary oscillations which reflect the physiological corticodiencephalic activity, a relationship has to be assumed. Frequencies and amplitudes of pupillary oscillations measured by means of Fourier analysis are modulated corticodiencephalically. Therefore, Alzheimer patients were compared to healthy controls with respect to their pupillary diameters and responses to an acetylcholine antagonist. Twenty-nine patients, aged between 55 and 85 years, suffering from mild to moderate Alzheimer’s disease (AD) and 29 normal controls of similar age (56–85 years) participated in the study. The cholinergic receptors of the pupil were blocked by the acetylcholine antagonist tropicamide. It could be assumed that the larger the pupillary dilatation, the larger the extent of cognitive deficits. Alzheimer patients show abnormal acetylcholine neurotransmission. Changes of pupillary diameter after instillation of 1 drop of 0.01% tropicamide solution were measured and Fourier analysis of pupillary oscillations was performed. Times of measurement were: 0 (baseline), 20, 40, 60, 80, and 100 min. After 4 min tropicamide was instilled. Forty min after the instillation of tropicamide into the left eye, the Alzheimer patients showed a pronounced dilatation of 41.57%. The dilatation in normal controls was 28.5%. Fourier analysis of pupillary oscillations (sum of frequency bands = power) demonstrated a marked deactivation (low amplitudes in low-frequency bands, but in contrast to our expectations no higher amplitudes in the higher frequency bands) in patients with AD which remained constant at all times of measurement. By means of discriminant analysis of pupillary diameter and pupillary oscillations (frequency band 0.00–1 Hz), 89.7% were correctly predicted to be Alzheimer patients, 89% to be normal controls.

The influence of restraint stress on potential aluminum (Al)-induced behavioral changes was assessed in CD-1 mice. Three groups of adult mice were given 0, 300 and 600 mg Al/kg body weight per day in drinking water for 2 weeks. One-half of the animals in each group were concurrently subjected to restraint stress during 1 h per day throughout the study. After cessation of treatment, open-field activity, active avoidance learning, and motor resistance and coordination of the animals were evaluated. At the end of the behavioral testing period, mice were killed and Al concentrations were determined in a number of tissues. There were no remarkable effects of Al, restraint stress or their combined administration on either open-field activity or on the number of avoidances in an automatic reflex conditioner. However, a lower motor resistance and coordination in a rotarod were observed following exposure to Al at 600 mg/kg/day, restraint alone or concurrent administration of Al (300 and 600 mg/kg/day) plus restraint stress. The levels of Al in whole brain and cerebellum were significantly enhanced in mice exposed to Al plus restraint. Although the present results scarcely show Al-induced neurobehavioral effects, the influence of restraint stress on Al levels in whole brain and cerebellum can be the basis for further studies on the potential role of this element in certain neurological disorders.

This study investigated the relationship between trait hostility and aspects of serotonergic function by assessing the prolactin (PRL) response to acute tryptophan depletion and enhancement in 28 healthy male volunteers. Serum PRL was assessed immediately before, and 4.5 h after, administration of an amino acid drink enhanced with, or depleted of, the 5-HT precursor tryptophan. Trait hostility and ΔPRL (value at 4.5 h minus baseline) correlated negatively following enhancement and positively following depletion, indicating that the higher the hostility the smaller the change in PRL in either direction. This is consistent with previous research reporting an association between aggression and blunted neuroendocrine responses to serotonergic agents. The results indicate the possibility that, in people high on hostility, part of the serotonergic pathway that leads to modulation of PRL release is characterised by a stage with either low capacity relative to input availability or a strong negative feedback component.

The study of hemispheric asymmetry in olfaction in human subjects has given rise to many publications, but the findings have often been contradictory. This study used bilateral electrodermal activity recordings with unilateral stimulation as a measure of functional hemispheric asymmetry. A specific odorant (lavender) was used by monorhinic (single nostril) stimulation on 30 dextral subjects (20 females and 10 males). Intraindividually, the results showed no difference between the two nostrils, but all subjects exhibited a constant direction of electrodermal asymmetry: 20 subjects systematically showed a greater response amplitude for the right hand and 10 subjects systematically showed a greater response amplitude for the left hand, whatever hemisphere stimulated.

The effects of the opioid fentanyl and low doses of alcohol on neuropsychological functions in healthy volunteers were measured. Twenty-four healthy male volunteers participated in this study. Two randomised placebo-controlled cross-over trials were conducted. In group 1, 6 subjects received fentanyl (0.2 µg/kg body weight) in the order of fentanyl/placebo and 6 subjects in the order of placebo/fentanyl. Group 2 received alcohol in a similar procedure by continuous intravenous infusion, leading to a blood alcohol concentration (BAC) of 0.03%. Impairment was measured via different neuropsychological tests. The results indicate that fentanyl in concentrations commonly used in out-patient surgical procedures produces pronounced cognitive impairment (auditory reaction time, signal detection, sustained attention, recognition) in comparison to placebo. After application of low doses of alcohol (BAC 0.03%) only visual reaction time was impaired in comparison to placebo.

The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.

The aim of the present study was to examine the possibility that the accumulation of life events is associated with low lymphoproliferative response to mitogens in undergraduate students. We also analyzed the possible interaction between life events and personality traits. Lymphocyte response to phytohemagglutinin (PHA) was lower in subjects with high life events compared to those with low levels. Introverted subjects were found to exhibit lower lymphocyte responses to PHA than those who were extraverted, and there was no interaction between the effect of introversion and life events on the proliferative capacity. Lymphocyte proliferation was low in subjects with high anxiety scores, whether they had high or low levels of life events. In the group with high scores on independence a high accumulation of life events was not associated with lower lymphoproliferation; while in the group with low scores it was, suggesting that independence buffers the association between life stress and lower cellular immunity.