Thermoregulatory, motor, behavioural, and nociceptive responses of rats to 3 long-acting neuroleptics

We investigated physiological effects of intramuscular injections of the following 3 long-acting neuroleptics commonly used in wildlife management: haloperidol (0.05, 0.1, and 0.5 mg/kg body mass), zuclopenthixol acetate (0.5, 1, and 5 mg/kg), and perphenazine enanthate (1, 3, and 10 mg/kg), in a rat model. Body temperature and cage activity were measured by intra-abdominal telemeters. Nociceptive responses were assessed by challenges to noxious heat and pressure. Haloperidol (0.5 mg/kg) produced a significant nocturnal hypothermia (p < 0.05) and decreased nighttime cage activity and food intake. Zuclopenthixol (5 mg/kg) significantly decreased nighttime body temperature and cage activity and, at 1 mg/kg and 5 mg/kg, significantly decreased food intake 5-17 h after injection (p < 0.05). Perphenazine (10 mg/kg) significantly decreased nighttime body temperature and cage activity and, at all doses, significantly decreased food intake 5-17 h after injection (p < 0.05). Significant analgesic activity was evident in rats given 5 mg/kg zuclopenthixol up to 40 h after injection, and 10 mg/kg perphenazine from 48 to 96 h after injection (p < 0.0001). Zuclopenthixol (5 mg/kg) and perphenazine (10 mg/kg) had significant antihyperalgesic activities at 16 h postinjection and 24-48 h postinjection, respectively (p < 0.0001). Haloperidol had no significant antinociceptive activity at doses tested. Motor function was impaired in rats given 0.5 mg/kg haloperidol, 5 mg/kg zuclopenthixol and 10 mg/kg perphenazine. Effects of long-acting neuroleptics on body temperature, feeding, and activity were short-lasted and should not preclude their use in wildlife. Antinociceptive actions were longer-lasting, but were nonspecific, and we recommend additional analgesics for painful procedures during wildlife management.     

Metabolism and thermoregulation in the Cabrera vole (Rodentia: Microtus cabrerae)

Metabolism and thermoregulation were studied for the first time in the Cabrera vole (Microtus cabrerae), an endemic and threatened rodent of the Iberian Peninsula. Low values of resting metabolic rate (RMR) were registered (1.13 mlO(2) g(-1) h(-1)) at the lower limit of the thermoneutral zone (TNZ) (around 33.5 degrees C). Body temperature increased near the TNZ up to 37.3 degrees C but remained stable, around 36 degrees C, at ambient temperatures below 25 degrees C. Values of thermal conductance remained quite stable at ambient temperatures of 10-25 degrees C (0.144-0.160 mlO(2) g(-1) h(-1) degrees C) and increased to 0.301 mlO(2) g(-1) h(-1) degrees C at 33.5 degrees C. Data revealed that M. cabrerae developed a highly adaptive ability of conserving energy and lowering the metabolic cost of thermoregulation at high ambient temperatures, allowing the body temperature to approximate that of the environment and exhibiting low resting metabolic rate and high conductance.     

Evaluation of miniature data loggers for body temperature measurement during sporting activities

We recorded body temperatures in four runners, two squash players and one swimmer at 1-min intervals using miniature data loggers. These single-channel loggers are small and light (25 g), and were easily carried by the athletes during their sporting activities. Wide-range loggers (-37 degrees C to +46 degrees C), which had a temperature resolution of 0.4 degrees C, were used to measure thigh skin temperature. Auditory canal temperature and rectal temperature were measured with narrow-range loggers (+34 degrees C to + 46 degrees C) which had a considerably higher resolution (0.04 degrees C). With the aid of visual analogue scales subjects reported that the thermometric equipment caused very little discomfort or impairment of exercise performance. Loggers connected to uncoated bead thermistors (used for skin and auditory canal temperatures) had a thermal time constant of 0.4 s, and that of the coated thermistors (rectal probes) was 6 s. We were able to waterproof the equipment and measure rectal temperature in a swimmer. Hot (35 degrees C) or cold (5 degrees C) ambient temperatures had an insignificant effect on the intrinsic accuracy of the data loggers, even when used without recalibration at those temperatures. We believe that miniature temperature loggers are convenient and accurate thermometers for use during sporting activities and may provide new insights into thermoregulation during exercise.     

Behavioral thermoregulation by hypoxic rats.

To address whether a shift in hypothalamic thermal setpoint might be a significant factor in induction of hypoxic hypothermia, behavioral thermoregulation was examined in 7 female Sprague-Dawley rats implanted with radiotelethermometers for deep body temperature (Tb) measurement in a thermocline during normoxia (PO2 = 125 torr) and hypoxia (PO2 = 60 torr). Normoxic rats (TNox) selected a mean ambient temperature of 19.7 +/- 1.4 (SE) degrees C and maintained Tb at 37.0 +/- 0.2 degrees C. Hypoxic rats selected a significantly higher ambient temperature (THox = 28.6 +/- 2.2 degrees C) but maintained Tb significantly lower at 35.5 +/- 0.3 degrees C. Without a thermal gradient (ambient temperature = 25 degrees C), Tb during hypoxia was 35.4 +/- 0.4 degrees C. The maintenance of a lower body temperature during hypoxia through behavioral thermoregulation despite having warmer temperatures available supports the hypothesis that the thermoregulatory setpoint of hypoxic rats is shifted to promote thermoregulation at a lower Tb, effectively reducing oxygen demand when oxygen supply is limited.     

Simple roost nests confer large energetic savings for sparrow-weavers

White-browed sparrow-weavers (Plocepasser mahali, body mass 40 g) are group-living passerines adapted to the semi-arid environment of north-eastern and south-western Africa. During winter, the nocturnal ambient temperature of these regions often falls below 0 degrees C. imposing conditions demanding an increase in thermoregulatory heat production. Individuals roost throughout the year in inverted U-shaped roost nests. We investigated the energetic advantages of roosting by measuring nest and ambient temperatures in the field, as well as the resting metabolic rate (RMR) of the birds. The sparrow-weavers exhibited a wide thermoneutral zone (13 degrees C - 32 degrees C). Although RMR at thermoneutrality (40.2 J g.h(-1)) conforms with those of other passerines. the value at 0 degrees C (74.8 J g.h(-1)) is significantly lower than expected. The slope of the line below the lower critical temperature is unexpectedly steep, however, and appears to cause the physiological requirement for nest roosting due to a high cost of thermoregulation at low temperatures, perhaps due to shivering or non-shivering thermogenesis. The nest temperature at 0 degrees C ambient is 5 degrees C. resulting in a saving of some 7% in the energy spent during winter nights when food resources are in short supply compared with the rest of the year.     

MK801 impairs thermoregulation in the heat

The effects of MK801 (dizocilpine), a glutamate NMDA receptor antagonist, on thermoregulation in the heat were studied in awake rats exposed to 40 degrees C ambient temperature until their body core temperature reached 43 degrees C. Under these conditions, MK801-treated rats exhibited enhanced locomotor activity and a steady rise in body core temperature, which reduced the heat exposure duration required to reach 43 degrees C. Since MK801-treated rats also showed increased striatal dopaminergic metabolism at thermoneutrality, the role of dopamine in the MK801-induced impairment of thermoregulation in the heat was determined using co-treatment with SCH23390, a dopamine D1 receptor antagonist. SCH23390 normalized the locomotor activity in the heat without any effect on the heat exposure duration. These results suggest that the MK801-induced impairment of thermoregulation in the heat is related to neither a dopamine metabolism alteration nor a locomotor activity enhancement.     

Growth rate and thermoregulation in reared king quails (Coturnix chinensis)

Growth rate was investigated in king quails between 1st and 60th day of life. Gompertz growth constants were 0.075 in males and 0.056 in females. Colonic temperature (Tb) was measured in quails divided into four age groups (1-3, 7-10, 16-19, and 44-59 days old) in ambient temperatures set separately for each group. Metabolic rate was measured only in 44-59-day-old birds. The mean value of the thermoneutral body temperature (Tb at TNZ) in the active phase in the youngest quails was 39.0 degrees C. In 44-59-day-old quails, the resting metabolic rate in the thermoneutral zone (RMR at TNZ) was on average 9.44 mW g(-1) (1.66 cm3 O2 g(-1)h(-1)), without sex-specific differences. No such differences were found in this age group neither in Tb at TNZ, nor in minimal thermal conductance (Cmin). However, differences were found in the rate of metabolic heat production below the thermoneutral zone, even when mass-independent units were used. The maximum metabolic rate (Mmax) in 2-month-old males was 34.08 mW g(-1) (5.98 cm3 O2 g(-1)h(-1)), while in females 29.73 mW g(-1) (5.21 cm3 O2 g(-1)h(-1)). Heat-stressed 44-59-day-old quails elevated their Tb to as much as an average 44.1 degrees C in Ta of about 45 degrees C. The obtained growth model and a gradual development of the body temperature regulation mechanism in king quails followed the known strategy of development, typical for precocial birds. The sexual size dimorphism in the studied quails did not result in differences in thermoregulation parameters between the sexes, except for the rate of metabolic rate below thermoneutral zone.     

Interactive effects of intracisternal oxytocin and other centrally active substances on colonic temperatures of mice

Oxytocin (OXY) administered intracisternally to adult male mice produced a significant dose-related (1-4 micrograms) increase in colonic temperatures at an ambient temperature of 25 degrees C. The maximal rise in temperature occurred 30 min after administration of the peptide. The interactive effects on colonic temperature of central OXY with equimolar amounts of neurotensin, bombesin or beta-endorphin or of 2 2 mg/kg of chlorpromazine were investigated. OXY significantly antagonized the hypothermia produced by all of these substances. Pretreatment of mice with haloperidol or naloxone failed to prevent OXY-induced hyperthermia. The hyperthermic action of OXY and the interactive effects of OXY with other peptides on thermoregulation may be physiologically significant during parturition and lactation.     

Energetics and thermoregulation during digging in the rodent tuco-tuco (Ctenomys talarum)

For subterranean rodents, searching for food by extension of the tunnel system and maintenance of body temperature are two of the most important factors affecting their life underground. In this study we assess the effect of ambient temperature on energetics and thermoregulation during digging in Ctenomys talarum. We measured VO2 during digging and resting at ambient temperature (Ta) below, within, and above thermoneutrality. Digging metabolic rate was lowest at Ta within the thermoneutral zone and increased at both lower and higher temperatures, but body temperature (Tb) remained constant at all Tas. Below thermoneutrality, the cost of digging and thermoregulation are additive. Heat production for thermoregulation would be compensated by heat produced as a by-product of muscular activity during digging. Above thermoneutrality, conduction would be an important mechanism to maintain a constant Tb during digging.     

Dopamine receptor blockade increases glandular kallikrein-like activity in the neurointermediate lobe of the rat pituitary

The effect of dopamine receptor blockers on glandular kallikrein-like activity in the neurointermediate lobe of the rat pituitary was examined. Male rats were given daily injections of haloperidol (2.5 mg/kg), perphenazine (5 mg/kg) or sulpiride (60 mg/kg) for 7 days. Homogenates of the neurointermediate lobe were prepared. Latent proteases were activated with trypsin and proteolytic activity was measured at 37 degrees C, pH 8.0 using chromogenic peptide substrates. All three dopamine receptor blockers produced about a 100% increase in glandular kallikrein-like activity. The results suggest that glandular kallikrein-like activity in the neurointermediate lobe is under inhibitory control by dopaminergic mechanisms.     

Endotoxin fever in the rat.

In rats intravenous injections of E. coli endotoxin at thermoneutral or slightly warmer environmental temperatures resulted in biphasic febrile response: two rises of temperature being separated by a transient fall. At an ambient temperature of 20 degrees C the change in body temperature still had a biphasic pattern, however, the fall was the dominant change. Each part of the response was the result of a coordinated reaction which involved heat production mechanisms (including interscapular and periaortic brown fat thermogenesis) and heat loss effectors (tail vasomotor changes) separately or in combination. Beside ambient temperature, the initial body temperature at the start of endotoxin action exerted an important role in determining which of the effector functions would be involved in the response.     

Regional blood flow changes in response to thermal stimulation of the brain and spinal cord in the Pekin duck

Summary In conscious Pekin ducks, carotid and sciatic blood flows, respiratory rate, core and skin temperatures were measured during selective thermal stimulations of the spinal cord and rostral brain stem in thermoneutral (20 °C) and warm (32 °C) ambient conditions.At thermoneutral ambient temperature selective heating of the spinal cord by 2–3 °C (to 43–44 °C) increased the carotid blood flow by 138% and the sciatic blood flow by 46%. Increase in blood flows was correlated with increased breathing rate and beak and web skin temperatures.Selective cooling of the spinal cord at warm ambient temperatures and panting reduced the blood flow in both arteries and decreased the breathing rate.Heating or cooling of the brain stem showed generally very weak but otherwise similar responses as thermal stimulation of the spinal cord. In one duck out of six there was a marked effect on regional blood flow during brain stimulation.The results show that thermal stimulation of the spinal cord exerts a marked influence on regional blood flow important in thermoregulation, whereas the lower brain stem shows only a weak thermosensitivity, and stimulation caused only small cardiovascular changes of no major consequence in thermoregulation.     

Torpor and hibernation in a basal placental mammal, the Lesser Hedgehog Tenrec Echinops telfairi

The patterns of heterothermy were measured in Lesser Hedgehog Tenrecs, Echinops telfairi, under semi-natural conditions in an outdoor enclosure during the austral mid-winter in southwestern Madagascar. The animals were implanted with miniaturized body temperature (Tb) loggers (iButtons) that measured body temperature every 42 min for 2 months (May and June). The tenrecs entered daily torpor on all 60 consecutive days of measurement, that is, on 100% of animal days, with body temperature closely tracking ambient temperature (Ta) during the ambient heating phase. The mean minimum daily Tb of the tenrecs was 18.44 +/- 0.50 degrees C (n = 174, N = 3), and never exceeded 25 degrees C whereas, apart from a few hibernation bouts in one animal, the mean maximum daily Tb was 30.73 +/- 0.15 degrees C (n = 167, N = 3). Thus during winter, tenrecs display the lowest normothermic Tb of all placental mammals. E. telfairi showed afternoon and early evening arousals, but entered torpor before midnight and remained in torpor for 12-18 h each day. One animal hibernated on two occasions for periods of 2-4 days. We consider E. telfairi to be a protoendotherm, and discuss the relevance and potential of these data for testing models on the evolution of endothermy.     

Thermoregulation, metabolism, and stages of sleep in cold-exposed men

Four naked men, selected for their ability to sleep in the cold, were exposed to an ambient temperature (Ta) of 21 degrees C for five consecutive nights. Electrophysiological stages of sleep, O2 consumption (VO2), and skin (Tsk), rectal (Tre), and tympanic (Tty) temperatures were recorded. Compared with five nights at a thermoneutral Ta of 29 degrees C, cold induced increased wakefulness and decreased stage 2 sleep, without significantly affecting other stages. Tre and Tty declined during each condition. The decrease in Tre was greater at 21 degrees C than at 29 degrees C, whereas Tty did not differ significantly between conditions. Increases in Tty following REM sleep onset at 21 degrees C were negatively correlated with absolute Tty. VO2 and forehead Tsk also increased during REM sleep at both TaS, whereas Tsk of the limb extremities declined at 21 degrees C. Unsuppressed REM sleep in association with peripheral vasoconstriction and increased Tty and VO2 in cold-exposed humans, do not signify an inhibition of thermoregulation during this sleep stage as has been observed in other mammals.     

Drug Interaction: Inhibitory Effect of Neuroleptics on Metabolism of Tricyclic Antidepressants in Man

Total urinary excretion of radioactivity after oral or intravenous administration of a test dose of ¹⁴C-imipramine was measured in eight patients. They were tested before, during, and after treatment with neuroleptics. Excretion diminished while the patients were being treated with perphenazine, haloperidol, or chlorpromazine, though not during flupenthixol treatment.Total urinary excretion of radioactivity and plasma levels of metabolites and unchanged drug were measured in five patients after a test dose of ¹⁴C-nortriptyline. Each patient was tested before and again during perphenazine treatment. In all patients perphenazine treatment caused: (1) decrease of total urinary excretion, (2) decreased plasma level of metabolites, and (3) increased plasma level of unchanged nortriptyline.These results indicate that neuroleptics inhibit the metabolism of tricyclic antidepressants in man.     

Effect of psychotropic drugs on cerebral Ca-activated ATPase in vitro

Neuroleptics, particularly haloperidol and perphenazine, inhibit the activity of brain Ca, Mg-ATPase to a greater extent than the antidepressants benactizin and amphetamine. The actomyosin-like Ca-ATPase is far less sensitive to the psychotropic drugs than Ca,Mg-AtPase. It is suggested that the inhibition of brain Ca,Mg-AtPase by neuroleptics may play a certain role in their antipsychotic action.     

Lower haematocrit,haemoglobin and red blood cell number in zebra finches acclimated to cold compared to thermoneutral temperature

Thermoregulation constitutes an important share of the energy budget of endotherms. Elevated thermoregulatory requirements must be met by oxygen supply through the blood, as heat is produced mainly via aerobic processes. In contrast to mammal studies, it remains unclear whether elevated thermoregulatory needs are followed by changes in haematological variables in birds. We investigated haematocrit (HCT), haemoglobin content per volume of blood (HGB), number of red blood cells (RBC_count), and size of the erythrocytes (RBC_area) in zebra finches Taeniopygia guttata acclimated to either cold or thermoneutral ambient temperatures under laboratory conditions. Seventy‐nine females were maintained for six weeks either in cold (T = +12°C) or thermoneutral (T = +32°C) ambient temperature prior to blood collection. On average, HGB, HCT and RBC_count were significantly lower by about 10% in cold acclimated compared to thermoneutral acclimated birds. Only RBC_area was not different between the two acclimation temperatures. Mean HCT, one of the most commonly measured haematological variable for example was 53 ± 0.9% (LSM ± SEM) in thermoneutral and 49 ± 0.8 % (LSM ± SEM) in cold acclimated zebra finches. On first sight, the observed lower values for three out of the four determined haematological variables in response to acclimation to cold question oxygen supply to be indeed a limiting factor for heat production. However, higher demands of oxygen supply due to increased thermoregulation in birds may instead require specific optimisation of blood viscosity and modulation by other cardiovascular properties. Nucleated red blood cells in birds may pose different strain on blood viscosity compared to non‐nucleated mammalian erythrocytes and explain the contrasting response in haematological variables to temperature acclimation between birds and mammals.     

Biochemical and immunological properties of related small ruminant trophoblast interferons

The objectives of this study were 1) to evaluate the biochemical and immunological properties of caprine interferon tau (cIFNtau), 2) to determine if intrauterine injection of recombinant ovine interferon tau (roIFNtau) extends CL life span in goats, and 3) to evaluate potential side effects of intramuscular (i.m.) administration roIFNtau. Caprine IFNtau was purified, and its effects on lymphocyte proliferation were evaluated. Incorporation of 3H-thymidine into newly synthesized DNA was suppressed (P<0.05) by cIFNtau. Spanish goats were also fitted with bilateral uterine catheters at Day 7 or 8 postestrus. The goats received twice-daily intrauterine injections of 100 microg roIFNtau (n = 4) or caprine serum proteins (n = 4) from Days 14 to 18 postestrus. Intrauterine injection of roIFNtau extended CL life span compared with that of control goats (26.4 +/- 1.7 vs 17.8 +/- 1.9 d, respectively; P<0.01). Potential side effects of intramuscular injections of roIFNtau were also evaluated. Goats received 0, 1, 2 or 4 mg of roIFNt on Days 10, 13, 16 or 19 of the estrous cycle. Treatment of goats with roIFN resulted in hyperthermia (P<0.01), with rectal temperatures of 40.5 degrees C recorded after 4 h and returning to normal (38.5 degrees C) after 24 h. Concomitant with the increase in rectal temperatures was a decrease (P<0.01) in plasma progesterone concentrations. Therefore, the tau interferons of goats and sheep have similar biological properties and roIFNtau has side effects associated with other classes of interferons.     

Static response in body temperature regulation of the euthermic warm-acclimated golden hamster (Mesocricetus auratus)

A characteristic feature of the body temperature regulation of euthermic golden hamsters is a great individual variability of body temperature in the thermoneutral zone. Resting values of the total metabolic rate (M) at ambient temperature 30-34 degrees C vary from 5.3 to 8.8 W.kg-1 between individuals, body temperature reaching 33.5-37.7 degrees C (subcutaneous temperature, Ts) and 35.4-39.0 degrees C (hypothalamic temperature, Th). The dependence of metabolic heat production on steady deviations of peripheral and central body temperature from the resting values in nonlinear in general, but the unknown functional relationship delta M = f (delta Th, delta Ts) can be replaced by a single linear regression function of Ts by neglecting the change of central body temperature: delta M = 2.14-2.00. delta Ts. Total body thermosensitivity of the golden hamster determined from steady changes of rectal temperature and metabolic rate after external cooling is -6.8 +/- 1.3 W.kg-1. degrees C-1.     

The physiology of hypothermia in the black-capped Chickadee,Parus atricapillus

Summary The shivering, body temperature, and metabolic response to stable and decreasing ambient temperature were measured in winter acclimatized Black-capped Chickadees,Parus atricapillus. Shivering activity, measured by duration and amplitude of bursts, increased curvilinearly from thermoneutral temperatures of 27°C down to 0°C. This parabolic shivering response may be a major component of the curvilinear response of metabolism to decreasing ambient temperature.Birds exposed to 0°C exhibited metabolism 32–45% lower than predicted for a 12-g homeotherm and body temperatures 10°C below the pre-experimental nocturnal body temperature. This hypothermia was not the result of a breakdown in thermoregulation, but was a controlled effort serving to reduce overnight energy expenditure. It is suggested that (1) hypothermia was achieved by decreased shivering by pectoral muscles during exposure to decreasing ambient temperatures, (2) the rate of body temperature decline was moderated by intermittent and reduced bursts during the cooling period, and (3) body temperature was maintained at a particular level during exposure to a stable low ambient temperature by intense bursts lasting one to three minutes.The physiology of hypothermia in chickadees is similar to torpor; however, chickadees did not arouse to a normal diurnal body temperature in the laboratory, and their hypothermia was not induced by inanition or prolonged exposure to cold, as reported for other species capable of torpor.