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Biomedical subjects

H R Lieberman

Publications and source records attributed to H R Lieberman.

At least 19 recordsLinked to original sources

Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats.

The calcium channel blocker nimodipine has been reported to improve cognitive performance in aged and brain-damaged animals. In the present study, the effects of nimodipine and placebo on spatial working memory and hippocampal acetylcholine were studied in young Fischer-344 rats. Nimodipine or placebo was administered via subcutaneously implanted, sustained-release pellets. Each active pellet contained 20 mg of nimodipine and released the drug over approximately 21 days. Two days after the drug or placebo pellets were implanted, training in the 8-arm radial maze started and continued for 12 days. Rats were required to learn a win-shift surgery. Nimodipine-treated animals learned the maze more rapidly than a placebo-treated group as indicated by the number of correct choices out of the first eight arms visited (p less than 0.001). Treated rats also made twice as many choices per unit time during the first week of training (p = 0.005). To assess hippocampal acetylcholine release, in vivo microdialysis was performed while animals were awake and unrestrained, 19-21 days after pellet implantation. A probe with a 3 mm semipermeable tip was placed in the hippocampus (CA1 and dentate gyrus), and individual microliters dialysate samples were collected at 2 microliters/min and immediately analyzed by high performance liquid chromatography with electrochemical detection. Significantly higher extracellular ACh levels were found in nimodipine-treated rats (71.4 +/- 3.6 nM; n = 4) compared to controls (52.5 +/- 2.5 nM; n = 5) (p = 0.003) and in another group of rats of the same age that received identical drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Doubly labeled water measurement of human energy expenditure during strenuous exercise.

The energy expenditures (EE) of 23 adult male Marines were measured during a strenuous 11-day cold-weather field exercise at 2,200- to 2,550-m elevation by both doubly labeled water (2H2 18O, DLW) and intake balance methods. The DLW EE calculations were corrected for changes in baseline isotopic abundances in a control group that did not receive 2H2 18O. Intake balance EE was estimated from the change in body energy stores and food intake. Body energy-store changes were calculated from anthropometric [-1,574 +/- 144 (SE) kcal/day] and isotope dilution (-1,872 +/- 293 kcal/day) measurements made before and after the field exercise. The subjects kept daily logbook records of ration consumption (3,132 +/- 165 kcal/day). Mean DLW EE (4,919 +/- 190 kcal/day) did not differ significantly from intake balance EE estimated from food intake and either anthropometric (4,705 +/- 181 kcal/day) or isotope dilution (5,004 +/- 240 kcal/day) estimates of the change in body energy stores. The DLW method can be used with at least the same degree of confidence as the intake balance method to measure the EE of active free-living humans.

Adult

Relationships between symptoms, moods, performance, and acute mountain sickness at 4,700 meters.

Ascents above 4,000 m adversely affect symptoms, moods, and performance and cause acute mountain sickness (AMS). It is assumed that individuals afflicted with AMS will be more susceptible to changes in these other parameters; however, previous studies have suggested that their time courses are different. This investigation analyzed the relationships between symptoms, moods, and performance and a measure of altitude sickness, the AMS-cerebral (AMS-C) factor of the environmental Symptoms Questionnaire (ESQ). We evaluated 20 male soldiers on 11 symptom, 13 mood, and 14 cognitive/motor performance measures after exposure to altitudes of 550 and 4,700 m for 5-7 h and a difference score was calculated for each measure. The difference scores for 70% of the symptom, 46.2% of the mood, and 28.6% of the performance measures were significantly correlated with the AMS-C difference score. The difference scores for each measure were then rank ordered (to standardize for differences across measures) and the sum of the ranks was calculated for each subject's symptoms, moods, and performance. The AMS-C factor score correlated significantly 0.90, 0.77, and 0.59 with these composite measures of symptoms, moods, and performance, respectively. Changes in AMS after 5-7 at 4,700 m were correlated best with changes in symptoms, then moods, and finally performance, suggesting that these parameters may be differentially affected at this point in time.

Adult

Circadian locomotor activity rhythms in Alzheimer's disease.

Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment.

Aged

Tyrosine pretreatment reverses hypothermia-induced behavioral depression.

Cold exposure accelerates the firing frequency of norepinephrine (NE) neurons, enhancing NE release and leading to NE depletion in specific regions of the brain. The accelerated firing activates the enzyme tyrosine-hydroxylase, making it more tyrosine sensitive. The reduction of brain NE is accompanied by a behavioral depression on the open field test. Two experiments were performed on adult male rats. First, it was determined whether systematic lowering of core body temperature produced behavioral depression in the swim test. Second, treatment with the NE precursor tyrosine was employed in an attempt to prevent hypothermia-induced behavioral depression. In Experiment 1, two levels of hypothermia were highly effective in producing behavioral depression in rats forced to swim in a narrow cylinder. In Experiment 2, treatment with tyrosine (400 mg/kg, IP) thirty minutes prior to the hypothermia procedure completely reversed the behavioral depression found in Experiment 1. Tyrosine administration did not significantly influence the rate of deep body cooling during the hypothermia treatment.

Animals

Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans.

Acutely stressful situations can disrupt behavior and deplete brain norepinephrine and dopamine, catecholaminergic neurotransmitters. In animals, administration of tyrosine, a food constituent and precursor of the catecholamines, reduces these behavioral and neurochemical deficits. Using a double-blind, placebo-controlled crossover design we investigated whether tyrosine (100 mg/kg) would protect humans from some of the adverse consequences of a 4.5 hour exposure to cold and hypoxia. Tyrosine significantly decreased symptoms, adverse moods, and performance impairments in subjects who exhibited average or greater responses to these environmental conditions. These results suggest that tyrosine should be evaluated in a variety of acutely stressful situations.

Adolescent

Aging, nutrient choice, activity, and behavioral responses to nutrients.

We directly measured nutrient consumption, activity patterns, and behavior in young volunteers and healthy elderly volunteers (N = 86) living in an identical environment. Compared to the young subjects, the elderly adults consumed fewer calories and less carbohydrate and fat, but not less protein, after adjustment for differences in body weight. Males of both ages consumed more protein than females after adjustment for body weight. All subjects snacked predominantly on carbohydrate-rich foods. The elderly subjects, however, consumed significantly fewer snacks than the young. Patterns of mood and activity also differed between age groups: the elderly volunteers were more active and alert than the young, especially early in the day, as measured by activity monitors and self-report questionnaires. We also examined the behavioral effects of high-protein and high-carbohydrate meals on these subjects because of the effects such meals can have on brain serotonin levels. The subjects ingested isocaloric carbohydrate- or protein-rich breakfasts and dinners and then participated in a series of behavioral tasks. Significant interactions between the type of meal consumed (protein versus carbohydrate) and the time at which they were ingested (breakfast versus dinner were observed. A protein meal consumed at breakfast induced more fatigue and sleepiness than an isocaloric carbohydrate meal; this was reversed in the evening when a carbohydrate meal induced more fatigue. Elderly subjects were less sensitive to sleepiness induced by carbohydrate in the evening. Overall, the young and old adults exhibited significant differences in calorie and carbohydrate intakes and also mood and activity, even when they chose their foods from an identical selection of food items and followed the same basic daily routines while living in a controlled study environment.

Adult

Increased activity and phase delay in circadian motility rhythms in geriatric depression. Preliminary observations.

Locomotor activity levels and rhythms of eight hospitalized geriatric unipolar depressed patients (DSM-III criteria) were compared with those of eight healthy elderly controls in a similar environment. Activity was measured using a wrist-worn electronic activity monitor with solid-state memory. Depressed patients had a 29% higher mean total 24-hour activity level, with no change in circadian amplitude or frequency. Daily peak activity (acrophase) averaged 2.05 hours later in depressed patients, with no overlap between the groups. The degree of phase delay correlated significantly with the 4 PM postdexamethasone serum cortisol level. These tentative findings suggest that elderly unipolar depressed patients have prominent chronobiological disturbances in the modulation of activity levels and possibly other physiological processes. These differ strikingly from reported disturbances in younger or bipolar depressed patients.

Adult

The effects of low doses of caffeine on human performance and mood.

Caffeine is thought to have stimulant-like behavioral effects on mood and performance. However few behavioral studies have examined this substance's acute effects when administered in a range of doses that include the low doses typically found in foods and over-the-counter drugs. We therefore gave single doses of caffeine (32, 64, 128 and 256 mg) to 20 healthy male subjects and assessed various aspects of performance and self-reported mood states, as well as plasma caffeine concentration. As little as 32 mg (which elevated plasma caffeine concentration to less than 1 microgram/ml), typical of the dose found in a single serving of a cola beverage, and less than that found in a single cup of coffee or a single dose of over-the-counter drugs, significantly improved auditory vigilance and visual reaction time. All other caffeine doses administered also significantly improved performance on these tests. No adverse behavioral effects, such as increased anxiety or impaired motor performance, were noted even at the highest dose administered.

Adolescent

A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol.

Since reports on the influence of melatonin (aMT) on the human endocrine system are scant and inconsistent, the effect of an acute, pharmacological dose of aMT on various hormone levels in healthy males was examined in 3 different experiments. Experiment I: 80 or 240 mg of crystalline aMT were administered per os to 8 volunteers. Before, during and after this treatment, serum levels of aMT, PRL, LH, FSH and testosterone were examined. Although aMT increased at least 1,500-fold over basal levels, only PRL was significantly and consistently elevated after aMT treatment, whereas serum levels of the other hormones were not altered. Experiment II: in 2 subjects, the pulsatile secretion pattern of LH was monitored for 6 h before and 6 h after aMT administration (240 mg p.o.). Neither the amplitude nor the frequency of LH pulses was influenced by the pineal hormone. Experiment III: in 14 volunteers, serum PRL, GH, TSH and cortisol concentrations were examined, once after oral administration of 240 mg aMT and once after placebo. Serum PRL levels were significantly higher after aMT than after placebo; GH showed a slight but not significant trend towards elevation after aMT, whereas other hormones were not altered. An acute pharmacological dose of aMT causes isolated elevation of serum PRL levels and may slightly increase GH. Hormones of the pituitary gonadal axis as well as TSH and cortisol are not altered by aMT.

Adult

The effects of caffeine and aspirin on mood and performance.

Caffeine, in addition to being a food constituent, is also a common analgesic adjuvant that is used in combination with aspirin in certain over-the-counter preparations. Caffeine has previously been shown to significantly improve certain aspects of human performance, particularly sustained vigilance, when administered in low and moderate doses (32 to 256 mg). We therefore attempted to determine whether caffeine, in the dose (64 mg) found in some over-the-counter drugs, retains this beneficial property when combined with aspirin. We also measured self-reported mood state, using various standardized questionnaires, since caffeine has been reported to have both beneficial and adverse effects on alertness and anxiety. We observed that caffeine (64 mg), when added to aspirin (800 mg), significantly improves vigilance performance and increases self-reported efficiency when compared with either placebo or aspirin alone. As previously reported, this caffeine dose alone significantly increased vigilance and decreased reaction time. No adverse effects of caffeine were detected on any of the parameters that were assessed. This study therefore demonstrated that the addition of caffeine to aspirin, in a dose commonly employed in over-the-counter drugs, has significant beneficial consequences with respect to mood and performance.

Adolescent

The composition of lunch determines afternoon plasma tryptophan ratios in humans.

It is well established that the ratio of the plasma tryptophan concentration to those of the other large neutral amino acids determines the transport of tryptophan into the brain. Brain tryptophan levels, in turn, control production of the neurotransmitter serotonin. Protein-rich meals, when consumed in the morning after an overnight fast, have been shown to decrease the plasma tryptophan ratio, while carbohydrate-rich meals have the opposite effect. We now show that these meals have similar effects when consumed for lunch, even if they are preceded by a small breakfast meal.

Adult

Changes in mood after carbohydrate consumption among obese individuals.

Two groups of obese individuals who consume excessive calories primarily as snack foods have been identified. Carbohydrate cravers consume most or all snacks as carbohydrate-rich foods despite the equal accessibility of protein-rich snacks. Noncarbohydrate cravers consume about equal amounts of protein- and carbohydrate-rich snack foods. Using standardized self-report questionnaires, we measured mood before and 2 h after consumption of a high-carbohydrate lunch (104 g CHO). Responses to the meal differed significantly: noncarbohydrate cravers reported feeling considerably less alert, more fatigued and sleepy, while carbohydrate cravers described little or no change in these aspects of mood. Moreover, noncarbohydrate cravers experienced an increase in depression, while carbohydrate cravers reported feeling less depressed. Findings suggest that snacking habits of obese individuals may be related to subsequent mood states.

Dietary Carbohydrates

Behavior, sleep and melatonin.

The focus of most behavioral studies on melatonin relate to sleep, arousal levels and circadian rhythms of alertness. It has also been suggested that melatonin administration can reduce anxiety (Golus and King, 1981), affect learning (Datta and King, 1980), and exacerbate symptoms in patients suffering from severe depression (Carman et al., 1976). For a variety of reasons the effects of exogenous melatonin on sleep and circadian rhythms seem most likely to reflect the actual physiological functions of the endogenous hormone; however, definitive relationships between melatonin secretion and these effects have not yet been established. Administration of melatonin to humans in pharmacologic doses produces acute hypnotic-like effects (Vollrath et al., 1981; Lieberman et al., 1984). Available evidence suggests that melatonin may participate in the physiological regulation of sleep, particularly in determining the phase of circadian rhythms of sleep and sleepiness (Redman et al., 1983; Wurtman and Lieberman, 1985).

Animals