Alerting effects of light

Light exerts powerful non-visual effects on a wide range of biological functions and behavior. In humans, light is intuitively linked with an alert or wakeful state. Compared to the effects of light on human circadian rhythms, little attention has been paid to its acute alerting action. Here I summarize studies from the past two decades, which have defined and quantified the dose (illuminance levels), exposure duration, timing and wavelength of light needed to evoke alerting responses in humans, as well as their temporal relationship to light-induced changes in endocrinological and electrophysiological sequelae of alertness. Furthermore, neuroanatomical and neurophysiological findings from animal studies elucidating a potential role of light in the regulation of sleep/wake states are discussed. A brief outlook of promising clinical and non-clinical applications of lights' alerting properties will be given, and its involvement in the design of more effective lighting at home and in the workplace will be considered.     

Neurotensin: distribution of hypothermic response in mammalian and submammalian vertebrates.

Neurotensin (NT), an endogenous tridecapeptide (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH), is a potent hypothermic agent after central administration in the mouse and rat. The purpose of the present investigation was to evaluate the effect of NT on thermoregulatory processes in a variety of mammalian and non-mammalian vertebrates: bluegill, frog, lizard, pigeon, ground squirrel, woodchuck, golden hamster, rabbit, guinea pig, gerbil, mouse, rat and monkey. All species except monkey were tested in two ambient environmental temperatures, 23°C and 4°C, except poikilotherms. Animals were injected intracisternally with microgram quantities of NT or vehicle, and body temperature was periodically assessed over a 2 hr period. NT did not induce a significant alteration in body temperature in any of the poikilotherms studied (bluegill, frog, and lizard). At 23°C NT produced a significant hypothermic response in the mouse, rat, gerbil, and monkey with no effect observed in the pigeon, rabbit, guinea pig, golden hamster, ground squirrel or woodchuck. At 4°C, NT produced a significant decrease in body temperature in the mouse, rat, gerbil, guinea pig and golden hamster with no effect evident in the pigeon, rabbit, ground squrrel or woodchuck. Species known to respond to cold by increasing metabolic rate (e.g. mouse and rat) appear to be most responsive to NT. The hypothermic activity of NT in a variety of mammals suggests that the peptide may play a role in thermoregulation.     

桂枝汤对体温双向调节作用的机理探讨──对下丘脑乙酰胆碱和去甲肾上腺素作用的影响

大鼠脑室注射去甲肾上腺素２０ｎｇ／只，仍快速引起体温下降，口饲给予１０ｇ／ｋｇ桂枝汤，能部分拮抗去甲肾上腺素的降温作用，大鼠脑室注射乙酰胆碱１ｍｇ／只，能使体温升高；口饲给予桂枝汤，能阻断其发热反应。结果提示，桂枝汤可能通过促进下丘脑中过量去甲肾上腺素或乙酰胆碱的灭活，拮抗或部分拮抗它们的降体温或发热作用。     

Modulation of morphine-induced Fos-immunoreactivity by the cannabinoid receptor antagonist SR 141716

A growing body of evidence suggests the existence of a functional interaction between opioid and cannabinoid systems. The present study further investigated this functional interaction by examining the combined effects of morphine and the cannabinoid receptor antagonist SR 141716 on Fos-immunoreactivity (Fos-IR), a marker for neural activation. Male albino Wistar rats were treated with SR 141716 (3 mg/kg, intraperitoneally), morphine HCl (10 mg/kg, subcutaneously), vehicle, or SR 141716 and morphine combined (n=6 per group). Rats were injected with morphine or its vehicle 30-min after administration of SR 141716 or its vehicle and perfused 3 h later. Locomotor activity and body temperature were both increased in the morphine-treated group and SR 141716 significantly inhibited these effects. Morphine increased Fos-IR in several brain regions including the caudate-putamen (CPu), cortex (cingulate, insular and piriform), nucleus accumbens (NAS) shell, lateral septum (LS), bed nucleus of the stria terminalis (BNST), median preoptic nucleus (MnPO), medial preoptic nucleus (MPO), hypothalamus (paraventricular, dorsomedial and ventromedial), paraventricular thalamic nucleus (PV), amygdala (central and basolateral nuclei), dorsolateral periaqueductal gray, ventral tegmental area (VTA), and Edinger–Westphal nucleus. SR 141716 alone increased Fos-IR in the cortex (cingulate, insular and piriform), NAS (shell), LS, BNST, hypothalamus (paraventricular, dorsomedial and ventromedial), PV, amygdala (central, basolateral and medial nuclei), VTA, and Edinger–Westphal nucleus. SR 141716 attenuated morphine-induced Fos-IR in several regions including the CPu, cortex, NAS (shell), LS, MnPO, MPO, paraventricular and dorsomedial hypothalamus, PV, basolateral amygdala, VTA, and Edinger–Westphal nucleus (EW). These results provide further support for functional interplay between the cannabinoid and opioid systems. Possible behavioural and physiological implications of the interactive effects of SR 141716 on morphine-induced Fos-IR are discussed.     

Diazepam withdrawal: effects of diazepam and gepirone on acoustic startle-induced 22 kHz ultrasonic vocalizations

It has proven difficult to demonstrate and study the anxiogenic quality of drug withdrawal states in animals. Ultrasonic vocalizations (USV) in response to acoustic startle stimuli have shown promise as a measure of affect and may represent distress responses during diazepam withdrawal. Three experiments evaluated the association between USV and distress by comparing the effects of diazepam as a prototypic benzodiazepine agonist and the putative anxiolytic gepirone with affinity for 5-hydroxytryptamine (5-HT_1A) receptors in naive and diazepam-withdrawn subjects. Adult male Long-Evans rats were exposed to acoustic startle sessions consisting of nine 105 dB and nine 115 dB stimuli. USV at 20–30 kHz were readily emitted during startle and often commenced after the third or fourth stimulus presentation. Acutely, intraperitoneal (IP) administration of diazepam (0.1–3 mg/kg) and gepirone (0.1–1 mg/kg) decreased USV dose-dependently without affecting the startle reflex; gepirone also decreased tail flick latency. Startle-induced USV were also sensitive to the anxiogenic effects of withdrawal from diazepam exposure (0, 2.5, 5, 10 mg/kg b.i.d. IP×5 days). Twenty-four hours after the last diazepam injection, rats were hyperreactive to startle stimuli and doubled their rate of USV over vehicle-treated controls. Gepirone (0.1–1 mg/kg IP), but not diazepam (3–20 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 10 mg/kg b.i.d. diazepam. Diazepam (2.5–10 mg/kg IP) antagonized the increased rate of USV in rats withdrawn from 2.5 mg/kg b.i.d. diazepam. USV induced by acoustic startle stimuli are sensitive to the anxiolytic effects of benzodiazepine and 5-HT_1A receptor agonists and permit the assessment of the anxiogenic properties of diazepam withdrawal. The potent effect of gepirone on USV suggests a serotonergic amelioration of the anxiogenic aspects of diazepam withdrawal.     

Effect of nomifensine and other antidepressant drugs on acetylcholine turnover in various regions of rat brain

Summary The thermoregulatory effects of dopamine (DA), given by intracerebroventricular (i.c.v.) injection to sheep, have been examined and compared with those of i.c.v. noradrenaline (NA).At ambient temperatures (T_a) of 20° and 30°C both DA (200 nmol·kg^–1) and NA (100 nmol·kg^–1) induced constriction of the ear vessels, a decrease in respiratory frequency and an increase in rectal temperature (T_r). At T_a of 10° and 0°C both substances caused a decrease in heat production and a fall in T_r.The DA receptor blocker spiroperone (30 nmol·kg^–1, i.c.v.), which itself had a vasodilatatory effect at 20°C T_a, blocked the peripheral vasoconstriction and slightly attenuated the rise in T_r normally caused by i.c.v. DA or NA at this T_a, but did not eliminate the suppression of respiratory frequency.During i.c.v. infusion, at 20°C T_a, with the DA--hydroxylase inhibitor FLA-63, the effect of i.c.v. DA or T_r was attenuated, while that of NA was enhanced.These results suggest that in the sheep central thermoregulatory system there are DA receptors which stimulate the pathway that controls peripheral vasomotor tone. The inhibitory effect of NA and DA on heat production and evaporative heat loss is probably mediated by noradrenergic receptors, which can also be activated by DA both directly and after its conversion to NA.     

Thermoregulation in hyperhydrated men during physical exercise

Summary The influence of hyperhydration on thermoregulatory function was tested in 8 male volunteers. The subjects performed cycle exercise in the upright position at 52%V _{O 2max} for 45 min in a thermoneutral (Ta=23° C) environment. The day after the control exercise the subjects were hyperhydrated with tap water (35 ml · kg^–1 of body weight) and then performed the same physical exercise as before.Total body weight loss was lower after hyperhydration (329±85 g) than during the control exercise (442±132 g),p<0.05. The decrease in weight loss after hyperhydration was probably due to a decrease in dripped sweat (58±64 and 157±101 g,p<0.05). With hyperhydration delay in onset of sweating was reduced from 5.8±3.2 to 3.7±2.0 min (p<0.05), and rectal temperature increased less (0.80±0.20 and 0.60±0.10° C,p<0.01). The efficiency of sweating was higher in hyperhydrated (81.4%) than in euhydrated subjects (57.1%),p<0,01. It is concluded that hyperhydration influences thermoregulatory function in exercising men by shortening the delay in onset of sweating and by decreasing the quantity of dripped sweat. As a result, the increases in body temperature in hyperhydrated exercising men are lower than in normally hydrated individuals.     

Integrated changes in regional circulatory activity evoked by thermal stimulation of the hypothalamus

Summary Radioactive microspheres were used to assess the influence of hypothalamic temperature on tissue blood flow and the regional distribution of cardiac output in conscious sheep chronically prepared with hypothalamic thermodes. Hypothalamic heating elicited panting in 6 animals, and in these, blood flow rate increased in respiratory muscles and decreased in the thyroids, kidneys, spleen and gut; cardiac output did not change, but was redistributed in a pattern similar to that seen during spinal cord heating, which differs from that which occurs during exposure to a warm environment. Four other animals did not pant in response to hypothalamic heating, but showed small but definite increases in capillary blood flow in skin of extremities. Reasons for the two different types of response to heating are discussed. The failure to detect increases in microsphere-measured extremity skin blood flow in the first group and only small changes in the second group above, despite the increased skin temperature always seen with hypothalamic heating, is attributed to specific influences of CNS stimulation on arteriovenous anastomoses.In 6 animals, hypothalamic cooling elicited visible shivering associated with increased oxygen consumption; blood flow rate decreased in skin and increased in respiratory and non-respiratory muscles, fat and the myocardium; cardiac output showed an increase and a redistribution similar to that which occurs during exposure to a cold environment.Arterial blood pressure was steady, but there were changes in regional vascular resistance. Therefore, and in view of other studies, the blood flow responses observed are attributed to regional differentiation of sympathetic activity.     

Ventilatory response of the panting dog to hypoxia

Summary The ventilatory response to isocapnic hypoxia was studied in anesthetized dogs during normothermia and thermally induced panting. In the normothermic dog, minute ventilation (_E), tidal volume (V _T) and respiratory frequency (f) did not vary significantly with changes ofPaO₂ above 80–90 mm Hg. Below this value, these three parameters increased substantially with progressively decreasingPaO₂. During panting the ventilatory response was triphasic: 1. withPaO₂ values above 90 mm Hg ventilation remained unaffected; 2. whenPaO₂ progressively decreased from 90 to 45 mm Hg, ventilation increased significantly over the levels of ventilation reached in response to heat alone; 3. withPaO₂ under 45 mm Hg ventilation abruptly decreased as compared to the second phase of the response.V _T increased significantly during the second and third segments as compared to the first. Respiratory frequency progressively decreased whenPaO₂ was under 60 mm Hg Isocapnic hypoxia suppressed thermally induced panting (tachypnea) but led to reduction of evaporative heat loss only at the lowest values ofPaO₂.Apparently, in the panting animal chemical control of respiration is set aside by the thermoregulatory control. However, chemical regulation of respiration may set aside the normal respiratory pattern of thermal polypnea in response to acute chemical stimuli, such as arterial hypoxia.