Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans.

Previous research suggests that the neuropeptide orexin A contributes to sympathetic blood pressure (BP) control inasmuch as hypothalamic injection of orexin A increases sympathetic vasomotor tone and arterial BP in rodents. In humans with narcolepsy, a disorder associated with loss of orexin-producing neurons, vasoconstrictive muscle sympathetic nerve activity (MSNA) is reduced. Since intranasally administered oligopeptides like orexin are known to modulate brain function, we investigated the effect of intranasal orexin A on vascular sympathetic baroreflex function in healthy humans. In a balanced, double-blind crossover study, orexin A (500 nmol) and placebo, respectively, were intranasally administered to 10 lean healthy males (age 25.8 ± 4.6 yr). MSNA was assessed microneurographically before and 30-45 min after either substance administration. Additionally, baroreflex was challenged via graded infusions of vasoactive drugs before and after substance administration. Baroreflex function was defined as the correlation of BP with MSNA and heart rate. Intranasal orexin A compared with placebo induced a significant increase in resting MSNA from pre-to postadministration [Δburst rate, orexin A vs. placebo: +5.8 ± 0.8 vs. +2.1 ± 0.6 bursts/min, P = 0.007; total activity 169 ± 11.5% vs. 115 ± 5.0%; P = 0.002]. BP, heart rate, and sympathovagal balance to the heart, as represented by heart rate variability (HRV), as well as baroreflex sensitivity during the vasoactive challenge were not altered. Intranasally administered orexin A acutely induced vasoconstrictory sympathoactivation in healthy male humans. This result suggests that orexin A mediates upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex feedback loop.NEW & NOTEWORTHY Our pilot study adds another important part to the complex network of neuroendocrine-sympathetic interaction. Our results demonstrate that intranasal orexin A elicits an excitatory effect on sympathetic vascular tone superordinate to mere baroreflex feedback regulation. This resetting of the baroreflex set point suggests an activation of hypothalamic core centers such as the paraventricular nucleus (PVN). The role of the orexinergic system in the development of neurogenic arterial hypertension warrants further investigations.

Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men.

BACKGROUND/OBJECTIVES: Animal studies and pilot experiments in men indicate that the hypothalamic neuropeptide oxytocin limits food intake, and raise the question of its potential to improve metabolic control in obesity. SUBJECTS/METHODS: We compared the effect of central nervous oxytocin administration (24 IU) via the intranasal route on ingestive behaviour and metabolic function in 18 young obese men with the results in a group of 20 normal-weight men. In double-blind, placebo-controlled experiments, ad libitum food intake from a test buffet was examined in fasted subjects 45 min after oxytocin administration, followed by the assessment of postprandial, reward-driven snack intake. Energy expenditure was repeatedly assessed by indirect calorimetry and blood was sampled to determine concentrations of blood glucose and hormones. RESULTS: Oxytocin markedly reduced hunger-driven food intake in the fasted state in obese but not in normal-weight men, and led to a reduction in snack consumption in both groups, whereas energy expenditure remained generally unaffected. Hypothalamic-pituitary-adrenal axis secretion and the postprandial rise in plasma glucose were blunted by oxytocin in both groups. CONCLUSIONS: Oxytocin exerts an acutely inhibitory impact on food intake that is enhanced rather than decreased in obese compared with normal-weight men. This pattern puts it in contrast to other metabolically active neuropeptides and bodes well for clinical applications of oxytocin in the treatment of metabolic disorders.

Role of γ-aminobutyric acid signalling in the attenuation of counter-regulatory hormonal responses after antecedent hypoglycaemia in healthy men.

The attenuated counter-regulatory response to hypoglycaemia after antecedent hypoglycaemic episodes has been observed in animals to be associated with an increase in γ-aminobutyric acid (GABA) signalling. We therefore tested the hypothesis that the pharmacological suppression of GABAergic activity during a repeated hypoglycaemic episode enhances counter-regulatory responses. Fourteen healthy men participated in two experimental sessions each comprising three insulin-induced hypoglycaemic episodes. Before the third hypoglycaemic episode, participants received the GABA-antagonistic drug modafinil (200 mg orally) and placebo, respectively. In the placebo condition, the secretion of norepinephrine, adrenocorticotropic hormone, cortisol and growth hormone, and the perception of neuroglycopenic symptoms were attenuated during the third as compared with the first hypoglycaemic episode (each p < 0.05). Modafinil reversed this effect for the noradrenergic response (p < 0.05), while not significantly altering the attenuation of other hormonal responses and symptom perception (p > 0.3). Our findings indicate that increased GABAergic transmission could contribute to aspects of the attenuated counter-regulatory response after recurrent hypoglycaemia in humans.

Acute sleep deprivation delays the glucagon-like peptide 1 peak response to breakfast in healthy men.

OBJECTIVE: Previous experiments have demonstrated that acute sleep loss impairs glucose homeostasis and increases food intake in humans. The incretin hormone glucagon-like peptide 1 (GLP-1) enhances postprandial insulin secretion and promotes satiety. Hypothesizing that the detrimental metabolic effects of sleep curtailment imply alterations in GLP-1 signaling, we investigated 24-h serum total GLP-1 concentrations during total sleep deprivation (TSD) and a normal sleep/wake cycle (comprising ∼8 h of sleep) in 12 healthy young men. METHODS: Sessions started at 1800 h, and subjects were provided with standardized meals. Assessments of serum GLP-1 took place in 1.5- to 3-h intervals, focusing on the response to breakfast intake (3.8 MJ). RESULTS: Across conditions, 24-h concentration profiles of GLP-1 were characterized by the expected postprandial increases (P<0.001). Although there were no differences in magnitude between conditions (P>0.11), the postprandial GLP-1 peak response to breakfast intake was delayed by ∼90 min following sleep loss in comparison with regular sleep (P<0.02). CONCLUSIONS: RESULTS indicate that acute TSD exerts a mild, but discernible effect on the postprandial dynamics of circulating GLP-1 concentrations in healthy men.

NMDA receptor blockade by memantine does not prevent adaptation to recurrent hypoglycaemia in healthy men.

AIMS: Recurrent hypoglycaemia leads to an attenuation of hypoglycaemic symptoms and hormonal counterregulatory responses. This phenomenon poses a severe problem in the treatment of patients with diabetes mellitus, but the underlying neuroendocrine mechanisms are unclear. On the basis of animal experimental findings, we hypothesized that counterregulatory attenuation represents a basic adaptive learning process relying on synaptic long-term potentiation or depression. If so, attenuation should be prevented by blocking glutamatergic N-methyl-D-aspartate (NMDA) receptors. METHODS: Sixteen healthy young men participated in two conditions, separated by 4 weeks. Participants received the NMDA antagonist memantine over 5 days (15 mg/day) in one condition and placebo in the other one. After 3 days of drug administration, participants underwent two hypoglycaemic clamps on day 4 and another one on day 5. We assessed blood concentrations of counterregulatory hormones (cortisol, ACTH, epinephrine, norepinephrine, growth hormone and glucagon) as well as subjective symptoms of hypoglycaemia and word-list recall as an indicator of short-term memory. RESULTS: Counterregulatory responses of all hormones as well as neuroglycopenic and autonomic symptom ratings showed robust attenuation following the third as compared to the first hypoglycaemia (p < 0.05). NMDA receptor antagonization by memantine impaired memory function but did not alter any neuroendocrine measure of counterregulatory attenuation (p > 0.17). CONCLUSIONS: Attenuation of the endocrine as well as symptomatic counterregulatory response to recurrent hypoglycaemia is not prevented by the NMDA receptor blocker memantine. Our results do not support the view that adaptation to repeated hypoglycaemia relies on NMDA receptor-mediated plastic processes involving long-term potentiation or depression.

The hedonic drive to consume palatable foods appears to be lower in gastric band carriers than in severely obese patients who have not undergone a bariatric surgery.

BACKGROUND: We have recently shown that severely obese patients display a markedly enhanced drive to consume palatable food, and that this hedonic hunger is reduced after gastric bypass surgery. Adjustable gastric banding is another frequently performed bariatric operation with unknown effects on hedonic hunger motivation. Here, we compared the level of hedonic hunger in patients who have undergone a gastric banding with that in severely obese patients who have not undergone a bariatric operation and nonobese controls. METHODS: In a cross-sectional case-control study, 116 gastric banding patients, 138 severely obese patients, and 133 nonobese controls were examined with the Power of Food Scale (PFS), a questionnaire that reliably measures an individual's motivation to consume highly palatable food. RESULTS: While the severely obese patients displayed markedly higher aggregated PFS scores and scores on the subdomain "generally available" and "physically present" food than the nonobese controls (all P < 0.001), the gastric banding patients showed significantly lower scores on all of these variables than the obese patients (all P < 0.001). However, the generally available food score was still higher in gastric banding patients than in the nonobese controls (P = 0.001). CONCLUSIONS: Data suggest that adjustable gastric banding may reduce the excessive appetite for palatable foods in severely obese patients. This suggestion needs to be confirmed in longitudinal studies.

Intranasal administration of insulin to the brain impacts cognitive function and peripheral metabolism.

In recent years, the central nervous system (CNS) has emerged as a principal site of insulin action. This notion is supported by studies in animals relying on intracerebroventricular insulin infusion and by experiments in humans that make use of the intranasal pathway of insulin administration to the brain. Employing neurobehavioural and metabolic measurements as well as functional imaging techniques, these studies have provided insight into a broad range of central and peripheral effects of brain insulin. The present review focuses on CNS effects of insulin administered via the intranasal route on cognition, in particular memory function, and whole-body energy homeostasis including glucose metabolism. Furthermore, evidence is reviewed that suggests a pathophysiological role of impaired brain insulin signaling in obesity and type 2 diabetes, which are hallmarked by peripheral and possibly central nervous insulin resistance, as well as in conditions such as Alzheimer's disease where CNS insulin resistance might contribute to cognitive dysfunction.

Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy.

BACKGROUND: The neuropeptides hypocretin-1 and -2 (hcrt-1 and -2, also known as orexin A and B) are crucially involved in the regulation of sleep/wake states. On the one hand, the sleep-wake disorder narcolepsy can be caused by an hcrt-1 deficiency. On the other, intracerebral administration of hcrt-1 produces an increase in wakefulness at the expense of REM sleep in normal and narcoleptic animals. In humans intranasal administration has been shown to effectively deliver neuropeptides directly to the central nervous system. We hypothesised that the intranasal application of hcrt-1 increases wakefulness and reduces REM sleep in the natural human hcrt-1 deficiency narcolepsy with cataplexy. METHODS: In this double-blind, random-order crossover, placebo-controlled, within-subject design study we administered human recombinant hcrt-1 (435 nmol) intranasally to eight subjects with narcolepsy with cataplexy before night sleep, followed by standard polysomnography. RESULTS: Although intranasal administration of hcrt-1 had no statistically significant effect on nocturnal wakefulness, we found that it reduced REM sleep quantity, particularly during the second half of the recording. Furthermore, intranasal hcrt-1 had a clear REM sleep stabilising effect and led to significantly reduced direct wake to REM transitions. CONCLUSION: In this pilot study we found, first, evidence that the intranasal administration of hcrt-1 has functional effects on sleep in narcolepsy with cataplexy. Our results may encourage the use of the intranasal approach in further studies on hypocretinergic sleep regulation and might also contribute to the future development of a causal treatment for narcolepsy with cataplexy.

Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

Research on functions and signalling pathways of insulin has traditionally focused on peripheral tissues such as muscle, fat and liver, while the brain was commonly believed to be insensitive to the effects of this hormone secreted by pancreatic beta cells. However, since the discovery some 30 years ago that insulin receptors are ubiquitously found in the central nervous system, an ever-growing research effort has conclusively shown that circulating insulin accesses the brain, which itself does not synthesise insulin, and exerts pivotal functions in central nervous networks. As an adiposity signal reflecting the amount of body fat, insulin provides direct negative feedback to hypothalamic nuclei that control whole-body energy and glucose homeostasis. Moreover, insulin affects distinct cognitive processes, e.g. by triggering the formation of psychological memory contents. Accordingly, metabolic and cognitive disorders such as obesity, type 2 diabetes mellitus and Alzheimer's disease are associated with resistance of central nervous structures to the effects of insulin, which may derive from genetic polymorphisms as well as from long-term exposure to excess amounts of circulating insulin due to peripheral insulin resistance. Thus, overcoming central nervous insulin resistance, e.g. by pharmacological interventions, appears to be an attractive strategy in the treatment and prevention of these disorders. Enhancement of central nervous insulin signalling by administration of intranasal insulin, insulin analogues and insulin sensitisers in basic research approaches has yielded encouraging results that bode well for the successful translation of these effects into future clinical practice.

Blocking AMPA receptor signalling by caroverine infusion does not affect counter-regulation of hypoglycaemia in healthy men.

AIMS/HYPOTHESIS: Glutamatergic pathways are assumed to play a critical role in the hormonal stress response to hypoglycaemia. In rats, glutamate signalling at the amino-3-hydroxy-5-methyl-4-isoxazol propionate (AMPA) receptor contributes to hormone release induced by behavioural stressors. We hypothesised that blocking the AMPA receptor by caroverine in healthy men would impair their perception of neuroglycopenia and thereby diminish hormonal counter-regulation as well as symptoms of hypoglycaemia, as a model of stress. METHODS: In a balanced double-blind study, two hypoglycaemic clamp sessions (mean blood glucose 2.4 mmol/l for 50 min) were performed in ten healthy men during intravenous administration of 80 mg caroverine or placebo. We assessed concentrations of counter-regulatory hormones as well as subjective symptoms related to hypoglycaemia. RESULTS: AMPA receptor antagonisation by caroverine did not influence the perception of neuroglycopenic and autonomic hypoglycaemia-associated symptoms (p > 0.39 for all). Notwithstanding, caroverine did increase basal and counter-regulatory glucagon secretion (p < 0.002) and slightly enhanced counter-regulatory growth hormone concentrations (p = 0.07). Counter-regulatory release of ACTH, cortisol, adrenaline (epinephrine) and noradrenaline (norepinephrine) did not differ between conditions (p > 0.11 for all). CONCLUSIONS/INTERPRETATION: Antagonising AMPA receptor signalling by caroverine infusion failed to diminish and even slightly amplified counter-regulatory hormone release during hypoglycaemia in healthy men. The discrepancy with previous findings in rats may be due to different dosages or administration routes and calls for further investigations on the role of AMPA receptor signalling in hypoglycaemia counter-regulation in humans.

Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial.

BACKGROUND: The 22q13 deletion syndrome (Phelan-McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. AIMS: To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome. METHODS: We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year. Short-term (during the first 6 weeks) and long-term effects (after 12 months of treatment) on motor skills, cognitive functions, or autonomous functions, speech and communication, emotional state, social behaviour, behavioural disorders, independence in daily living and education were assessed. RESULTS: The children showed marked short-term improvements in gross and fine motor activities, cognitive functions and educational level. Positive long-term effects were found for fine and gross motor activities, nonverbal communication, cognitive functions and autonomy. Possible side effects were found in one patient who displayed changes in balance, extreme sensitivity to touch and general loss of interest. One patient complained of intermittent nose bleeding. CONCLUSIONS: We conclude that long-term administration of intranasal insulin may benefit motor development, cognitive functions and spontaneous activity in children with 22q13 deletion syndrome.

Short-term nocturnal hypoglycaemia increases morning food intake in healthy humans.

AIMS: Hypoglycaemia during wakefulness increases hunger and food intake. Patients with Type 1 diabetes mellitus are at high risk of recurrent hypoglycaemia and weight gain. Given the background of frequent hypoglycaemic episodes during night-time sleep in diabetic patients, we investigated morning food intake after nocturnal hypoglycaemia. METHODS: We tested 16 healthy normal-weight subjects (eight women) on three nights. A linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion immediately after sleep onset ('early hypo') or after about 3.5 h of sleep ('late hypo'). On a control night, no hypoglycaemia was induced. Spontaneous food intake at a breakfast buffet was registered on the subsequent morning. RESULTS: Compared with the control condition (700 +/- 93 kcal), subjects ate more after 'late hypo' (867 +/- 108 kcal; P = 0.041), but not after 'early hypo' (852 +/- 111 kcal; P = 0.130). Analyses of macronutrient fractions revealed that in comparison with the control condition, subjects ate significantly more carbohydrates after both 'late hypo' (277 +/- 25 kcal vs. 206 +/- 23 kcal, P < 0.001) and 'early hypo' (245 +/- 23 kcal, P = 0.048), with this effect being more pronounced after late than early nocturnal hypoglycaemia (P = 0.026). CONCLUSIONS: In healthy subjects, nocturnal hypoglycaemia during sleep stimulates spontaneous food intake the following morning, with carbohydrate intake being especially affected. Effects were more pronounced after 'late hypo', suggesting the influence of temporal dynamics. Although healthy non-diabetic subjects were studied, similar mechanisms may contribute to the frequently observed body weight gain in insulin-treated diabetic patients.

Obese men respond to cognitive but not to catabolic brain insulin signaling.

CONTEXT AND OBJECTIVE: Insulin acts in the brain to reduce food intake and body weight and is considered a major adiposity signal in energy homeostasis. In normal-weight men, intranasal insulin administration reduces body fat and improves declarative memory. The present experiments aimed to generalize these findings to obese patients, with a view to evaluate the therapeutic potential of the compound. DESIGN, SUBJECTS AND MEASUREMENTS: Insulin and placebo, respectively, were intranasally administered four times a day (amounting to 160 IU day(-1)) over 8 weeks to two groups of 15 obese men each. RESULTS: Contrasting with the catabolic effects in normal-weight men, insulin treatment did not induce any significant reduction of body weight (P>0.50) and body fat (P>0.44) in the obese subjects. However, in accordance with the effects in normal-weight men, declarative memory and mood were improved (P<0.05) and hypothalamic-pituitary-adrenal axis activity as assessed by circulating ACTH (P<0.01) and cortisol levels (P<0.04) was reduced. CONCLUSIONS: Our results indicate that in obese men, intranasal insulin is functionally active in the central nervous system but fails to affect the neuronal networks critically involved in body weight regulation. We conclude that obesity in men is associated with central nervous resistance to the adiposity signal insulin. This defect likely contributes to the persistence of obesity in spite of elevated levels of circulating insulin in obese patients.

Plasma glucagon decreases during night-time sleep in Type 1 diabetic patients and healthy control subjects.

AIMS: In Type 1 diabetes mellitus (T1DM), the glucagon response to hypoglycaemia is known to disappear within a few months after the onset of the disease, whereas the response to other stimuli remains intact. The dynamics of spontaneous glucagon release have rarely been assessed. We monitored spontaneous glucagon release in T1DM patients and healthy subjects during a 7-h period of night-time sleep. METHODS: Measurements were made in 14 T1DM patients and 14 control subjects matched for age, gender and body mass index after one night's adaptation in our laboratory. Circulating glucose, insulin and glucagon concentrations were measured at 30-min intervals. In diabetic patients, hypoglycaemia (< 3.9 mmol/l) was avoided by infusion of glucose whenever necessary. RESULTS: During the entire night, plasma glucose and serum insulin levels were higher in T1DM patients than in healthy subjects (P < 0.03 and P < 0.001, respectively). Plasma glucagon concentrations decreased throughout the night in both groups (P < 0.001). Glucagon levels were similar in T1DM patients and healthy subjects (P > 0.87). The duration of diabetes (less and more than 5 years) did not affect glucagon secretion (P > 0.87). CONCLUSIONS: Plasma glucagon levels decrease significantly during night-time sleep in healthy control subjects. This nocturnal decrease is preserved in T1DM patients regardless of the duration of diabetes. These observations point to distinct nocturnal regulation of spontaneous glucagon release that does not depend on circulating glucose and insulin levels and is unaltered in T1DM patients.

Mood and cognitive functions during acute euglycaemia and mild hyperglycaemia in type 2 diabetic patients.

INTRODUCTION: Hyperglycaemia at levels above 15 mmol/l has been shown to impair cognitive functions in type 2 diabetic patients, while effects of mild hyperglycaemia and acute euglycaemia on mood and cognition have rarely been compared. We examined mood and cognitive functions in patients with T2DM during acute euglycaemia in comparison with moderate hyperglycaemia. METHODS: One euglycaemic (5 mmol/l) and one hyperglycaemic clamp (10.5 mmol/l) of 90 min each were performed in 15 T2DM patients in a balanced, single-blind, within-subject comparison. Mood, cognitive functions (assessed via short-term memory and attention tests) and symptoms related to glycaemic changes were assessed during a baseline period and during both glycaemic plateaus. In addition, patients estimated their blood glucose level and counterregulatory hormones were measured. RESULTS: None of the assessed aspects of cognitive functions differed between conditions (all p > or = 0.2). Patients rated higher on the well-being scale (p=0.04) and tended to feel less anger (p=0.08) during hyperglycaemia. Self-estimated blood glucose levels were higher during the hyper- than euglycaemic condition (8.6 +/- 2.5 vs 7.2 +/- 1.2 mmol/l; p<0.05) although most individual estimations did not match the actual glucose levels. Counterregulatory hormone levels did not differ (all p>0.25). CONCLUSIONS: Data indicate that T2DM patients are not cognitively impaired by moderate hyperglycaemia (10.5 mmol/l), pointing to the possibility of a glycaemic threshold for cognitive impairments at higher glycaemic levels.

Post-dural puncture headache in young adults: comparison of two small-gauge spinal catheters with different needle design.

BACKGROUND: To reduce the risk of post-dural puncture headache (PDPH) in continuous spinal anaesthesia, small-gauge spinal catheter systems with different techniques of dural perforation have been developed. METHODS: Two systems, the catheter through-needle technique (MicroCatheter, Portex, UK) and the catheter over-needle technique (22G Spinocath, B. Braun, Germany), were used in 18 young healthy volunteers (age 18-30 yr), who were enrolled in a neuroendocrinological investigation for analysis of neuropeptides in cerebrospinal fluid (CSF). After intermittent sampling of CSF (17 x 0.5 ml over 4 h), the catheter was removed and the development of PDPH and pain intensity were documented prospectively by the subjects in a standardized headache assessment (11-point numerical rating scale [NRS]). RESULTS: The study revealed a high overall incidence of PDPH (78%) with no significant differences between groups (P=0.26). However, the over-needle group showed a significantly shorter duration of PDPH (2.4 [SD 2.3] vs 5.1 [3.1] days, P=0.050) and lower maximum pain intensity (3.1 [2.9] vs 7.3 [3.4] NRS, P=0.014) than the through-needle group. CONCLUSIONS: The results demonstrate a potential benefit of the catheter over-needle technique for the reduction of the duration and intensity of PDPH.

NPY attenuates positive cortical DC-potential shift upon food intake in man.

Previous studies have shown that the regulation of hunger and satiety is accompanied by coordinate changes in cortical excitability. Starved subjects show a transient negative shift in the scalp-recorded cortical direct current (DC-)potential in the beginning of eating, indicating increased cortical excitability. With increasing satiety, the DC negativity becomes soon replaced by a reward related positive potential shift. Neuropeptide Y (NPY) is known from animal studies to increase food intake and induce weight gain, which might result from increasing hunger drive or reducing satiety. Here we investigated whether NPY affects the cortical sequelae of hunger and satiety regulation as reflected by cortical DC-potentials in man. DC-potentials were recorded over frontal (Fz, F3, F4), central (Cz, C3, C4) and parietal (Pz, P3, P4) electrode positions in 14 subjects who had abstained from eating for 15 h and who were intranasally administered 50 nmol of NPY and placebo 20 min prior to recordings. After a 3-min baseline epoch, subjects consumed 400 ml of liquid food within 5 min. Recordings ended 7 min after food consumption. In the placebo condition during food intake, with some delay a positive DC-potential shift developed which was most pronounced over frontal and central areas and reached maximum values 0-3 min after food consumption. NPY reduced this satiation associated positive shift (p<0.05) over all areas except P3 and Pz. Data suggest that NPY exerts its orexigenic influence by attenuating mechanisms of satiation.

EEG synchronization upon reward in man.

OBJECTIVES: It was tested whether reward in humans is associated with EEG synchronization similar to that seen in animals. METHODS: In two experiments (I and II) the EEG was recorded from frontal, central, and parietal positions before, during, and after drinking or oral stimulation. In Experiment I, subjects (n=11) who had either been thirsty for 16h or had quenched thirst before recordings, drank 400ml of water. In Experiment II, thirsty subjects (n=11) either drank 400ml of water or sucked on a soother. The recording epochs included a 3min baseline, an interval of about 5min during which subjects drank or sucked on the soother, and a 7min post-drinking interval. RESULTS: During the drinking epoch, beta band-power (12-30Hz) was enhanced in both conditions of Experiment I and II, respectively. In Experiment I, after drinking, lower alpha power (8-10Hz) was higher when subjects were thirsty than when they were not. Lower alpha was also enhanced in the post-drinking interval of both conditions of Experiment II, and after sucking, lower alpha synchronization was in addition accompanied by increased theta activity (4-8Hz). CONCLUSIONS: Increased beta activity during drinking and sucking in thirsty subjects presumably reflects non-specific activation related to the motivational strength of sensorimotor regulation during consumatory behavior. The thirst dependent lower alpha synchronization after drinking, generated not only by water consumption but also by surrogate oral stimuli, can be considered a reflection of the drive reducing and rewarding qualities of oral stimulation and consumatory behavior.

Drinking related direct current positive potential shift in the human EEG depends on thirst.

Scalp recorded direct current (DC)-potential shifts were examined in 11 human subjects who had either thirsted for 16 h or had quenched thirst before recordings. The recording epoch included a 3-min baseline, an interval of about 5 min during which subjects drank 400 ml of water, and a 7-min post-drinking interval. Consistent with previous data, when thirsty, subjects displayed a widespread negative DC-potential shift during drinking which was replaced by a positive DC shift at the transition to the post-drinking interval. The positivity after drinking lasted for about 2 min and averaged 146 microV at frontal recording sites. Quenching thirst before recordings reduced the positive DC-potential shift upon drinking, whereas changes in preceding drinking related DC negativity appeared to be secondary. The post-drinking positive DC-potential shift depending on the subject's motivational state can be considered an indicator of reward associated with quenching thirst, pointing to a lowered frontocortical excitability during reward.