Severe Cold Stress Research Articles

Cancer mortality in women and men who survived the siege of Leningrad (1941–1944)

The population of Leningrad suffered from severe starvation, cold and psychological stress during the siege in World War II in 1941-1944. We investigated the long-term effects of the siege on cancer mortality in 3,901 men and 1,429 women, born between 1910 and 1940. All study subjects were residents of St. Petersburg, formerly Leningrad, between 1975 and 1982. One third of them had experienced the siege as children, adolescents or young adults (age range, 1-31 years at the peak of starvation in 1941-1942). Associations of siege exposure with risk of death from cancer were studied using a multivariable Cox regression, stratified by gender and period of birth, adjusted for age, smoking, alcohol and social characteristics, from 1975 to 1977 (men) and 1980 to 1982, respectively (women), until the end of 2005. Women who were 10-18 years old at the peak of starvation were taller as adults (age-adjusted difference, 1.7 cm; 95% CI, 0.5-3.0) and had a higher risk of dying from breast cancer compared with unexposed women born during the same period (age-adjusted HR, 9.9; 95% CI, 1.1-86.5). Mortality from prostate cancer was nonsignificantly higher in exposed men. The experience of severe starvation and stress during childhood and adolescence may have long-term effects on cancer in surviving men and women.

Characterization of transcription factor gene SNAC2 conferring cold and salt tolerance in rice

Plants respond to adverse environment by initiating a series of signaling processes including activation of transcription factors that can regulate expression of arrays of genes for stress response and adaptation. NAC (NAM, ATAF, and CUC) is a plant specific transcription factor family with diverse roles in development and stress regulation. In this report, a stress-responsive NAC gene (SNAC2) isolated from upland rice IRA109 (Oryza sativa L. ssp japonica) was characterized for its role in stress tolerance. SNAC2 was proven to have transactivation and DNA-binding activities in yeast and the SNAC2-GFP fusion protein was localized in the rice nuclei. Northern blot and SNAC2 promoter activity analyses suggest that SNAC2 gene was induced by drought, salinity, cold, wounding, and abscisic acid (ABA) treatment. The SNAC2 gene was over-expressed in japonica rice Zhonghua 11 to test the effect on improving stress tolerance. More than 50% of the transgenic plants remained vigorous when all WT plants died after severe cold stress (4-8 degrees C for 5 days). The transgenic plants had higher cell membrane stability than wild type during the cold stress. The transgenic rice had significantly higher germination and growth rate than WT under high salinity conditions. Over-expression of SNAC2 can also improve the tolerance to PEG treatment. In addition, the SNAC2-overexpressing plants showed significantly increased sensitivity to ABA. DNA chip profiling analysis of transgenic plants revealed many up-regulated genes related to stress response and adaptation such as peroxidase, ornithine aminotransferase, heavy metal-associated protein, sodium/hydrogen exchanger, heat shock protein, GDSL-like lipase, and phenylalanine ammonia lyase. Interestingly, none of the up-regulated genes in the SNAC2-overexpressing plants matched the genes up-regulated in the transgenic plants over-expressing other stress responsive NAC genes reported previously. These data suggest SNAC2 is a novel stress responsive NAC transcription factor that possesses potential utility in improving stress tolerance of rice.

Blood pressure, hypertension and mortality from circulatory disease in men and women who survived the siege of Leningrad

The population of Leningrad suffered from severe starvation, cold and psychological stress during the siege in 1941-1944. We investigated long-term effects of the siege on cardiovascular risk factors and mortality in surviving men and women. 3905 men born 1916-1935 and 1729 women born 1910-1940, resident in St Petersburg (formerly Leningrad) between 1975 and 1982, of whom a third experienced the siege as children, adolescents or young adults, were examined for cardiovascular risk factors in 1975-1977 and 1980-1982 respectively and followed till end 2005. Effects of siege exposure on blood pressure, lipids, body size, and mortality were studied in multivariate analysis stratified by gender and period of birth, adjusted for age, smoking, alcohol and social characteristics. Women who were 6-8 years-old and men who were 9-15 years-old at the peak of starvation had higher systolic blood pressure compared to unexposed subjects born during the same period of birth (fully adjusted difference 8.8, 95% CI: 0.1-17.5 mm Hg in women and 2.9, 95% CI: 0.7-5.0 mm Hg in men). Mean height of women who were exposed to siege as children appeared to be greater than that of unexposed women. Higher mortality from ischaemic heart disease and cerebrovascular disease was noted in men exposed at age 6-8 and 9-15, respectively. The experience of severe stress and starvation in childhood and puberty may have long-term effects on systolic blood pressure and circulatory disease in surviving men and women with potential gender differences in the effect of siege experienced at pre-pubertal age.

Basal metabolic rate in the Yakut (Sakha) of Siberia

Human indigenous circumpolar populations have elevated basal metabolic rates (BMRs) relative to predicted values; this metabolic elevation has been postulated to be a physiological adaptation to chronic and severe cold stress. The present study examines BMR in the Yakut, an indigenous high-latitude population from the Sakha Republic of Russia to determine (1) whether the Yakut show evidence of an elevated BMR, (2) if the Yakut display evidence of age-related changes in BMR, and (3) whether lifestyle differences influence BMR. BMR was measured during the late summer in 75 women and 50 men (ages 18-56 years) from the Siberian village of Berdygestiakh. Measured BMR (+/- SEM) of the entire sample was significantly elevated (+6.5%) compared to predictions based on body mass (6,623.7 +/- 94.9 vs. 6,218.2 +/- 84.7 kJ/day; P < 0.001). Additionally, measured BMR for the entire sample was significantly higher than predictions based on fat-free mass (+20.8%) and surface area (+8.9%). Males and females both showed significant elevations relative to all three standards. The elevated BMR of the Yakut does not appear to be attributable to extreme levels of protein, since the Yakut consume a mixed diet with a substantial proportion of carbohydrates. No significant age-related changes in BMR were found when controlled for body composition. No significant relationship was found between lifestyle variables and BMR, suggesting the possibility of a genetic or developmental mechanism. This study provides additional evidence of metabolic elevation in indigenous circumpolar groups and has important implications for estimating the nutritional requirements of these populations.

Acute and long‐term effects of winter swimming and whole‐body cryotherapy on plasma antioxidative capacity in healthy women

The effects of severe cold stress on total peroxyl radical trapping antioxidant capacity of plasma (TRAP) were studied in two groups of healthy women: a whole‐body cryotherapy group (WBC, n = 10) and a winter swimming group (WS, n = 10). The biovariability of TRAP values was also analysed. The WBC group was exposed to −110°C for 2 min, whereas the exposure for the WS group lasted 20 s in ice‐cold water. Sessions were organized three times per week for 12 weeks. Blood specimens were collected at 2, 4, 8 and 12 weeks at rest, 2 and 35 min after the cold exposures and at the corresponding times without cold exposure on a separate day. Conventional methods were used to determine TRAP values. The between‐subject variation was 13.6% and the within‐subject variation 6.4%. The index of individuality was 0.46, and the index of heterogeneity was 0.079. These results indicate a marked heterogeneity among subjects. During the first 4 weeks, the mean TRAP value significantly increased at 2 min after cold exposure in the WBC group, returning to baseline 35 min after the exposure. Similar changes were observed in the WS group. However, all changes due to cold were relatively mild (<5%). After 4 weeks no changes in TRAP values after the cold exposures were noticed and no long‐term changes in basal TRAP values were observed. In the main, regular WBC and WS do not seem to be harmful as far as plasma antioxidative capacity is concerned.

Thermal sensation and comfort in women exposed repeatedly to whole-body cryotherapy and winter swimming in ice-cold water

Whole-body cryotherapy (WBC; −110 °C) and winter swimming (WS) in ice-cold water are severe ambient cold exposures, which are voluntarily practiced by humans in minimal clothing. The purpose was to examine thermal sensation and thermal comfort associated with WBC and WS. Twenty women similar in body mass index, age, physical activity, and use of hormonal contraception were pairwise randomized either to the WBC group or the WS group. The duration of each WBC exposure was 2 min, which was repeated three times per week for 3 months (13 weeks). Similar exposure frequency was used for the WS group, but each exposure lasted 20 s in outdoor conditions. Thermal sensation and comfort were asked with standard scales. After WBC, 65% of the thermal sensation votes were ‘neutral’ or ‘slightly cool.’ After WS, 81% of the thermal sensation votes were ‘warm,’ ‘neutral,’ or ‘slightly cool.’ Majority of comfort votes immediately after exposures in WBC group (98%) and in the WS group (93%) were ‘comfortable’ or ‘slightly uncomfortable.’ Thermal sensation and comfort became habituated in both groups at an early stage of trials, but the changes were less conclusive in WS group due to variable conditions outdoors. In the WBC group, cold sensation was less intense already after the second exposure. In conclusion, repeated exposures to WBC and WS in healthy women were mostly well tolerated and comfortable. The results indicate that during repeated severe whole-body cold stress of short duration, thermal sensation and comfort become habituated during the first exposures.

The influence of climatic conditions on physiological and behavioural parameters in dairy cows kept in open stables

AbstractThis study aimed to assess whether cows are able to cope with the range of climatic conditions they are exposed to in open stables on commercial farms in central Europe. On each of four farms, ten lactating cows were observed over a total of five weeks in winter, spring and summer. Based on continuous measurements of air temperature (–13·8 to 28·7ºC) and relative air humidity (0·26 to 0·99), a mean value of a temperature humidity index (THI) was calculated for each farm and each observation day for night and day.THI had significant effects on skin temperature and body surface temperature (infra-red thermography) both during night and day. Rectal temperature, duration of lying and cortisol concentration in the milk was significantly affected by THI during the day but not during the night. Heart rate and frequency of lying did not significantly covary with THI. Differences between farms and interactions between THI and farm were significant for most parameters. These results suggest that the climatic conditions during the day induced stronger thermoregulatory responses than the conditions during the night. Within the measured range of climatic conditions the cows were hardly exposed to severe cold or heat stress.

Effect of cold stress on broilers selected for resistance or susceptibility to ascites syndrome

Genetic selection for an ascites-resistant line of broilers is seen as a permanent solution to the ascites problem. Ascites-resistant and ascites-susceptible lines have been developed using sire family selection based on mortality data taken from siblings reared in a hypobaric chamber (simulated 2,900 m above sea level). The relaxed line is representative of the original commercial pureline stock randomly mated with no artificial selection pressure. The objectives of this study were to evaluate the differences between the lines when reared in floor pens and subjected to an ascites-inducing cold stress. Seven hundred eighty three straight run broilers were reared in floor pens at local elevation (390 m above sea level). Feed and water were available ad libitum. Birds were brooded at 32 C during the first week. The second week birds were maintained at 30 degrees C. Cold stress was applied for the remaining 4 wk at 14 degrees C. Mortalities were necropsied daily to determine cause of death. Birds and feed were weighed weekly. At 6 wk, five birds per pen were bled, and half the survivors in each pen (8 to 15 birds) were killed, necropsied, and scored for ascites. Blood gases, clinical chemistries, and blood cell counts were taken. Liver, spleen, split heart, and lung weights were recorded. Body weights were not different among the resistant, susceptible, and relaxed lines (P < 0.05). Feed conversion was better in the resistant line when compared to the susceptible and relaxed lines (P < 0.05). Ascites incidence, as measured by mortality and lesion score at necropsy, was higher in the susceptible and relaxed lines when compared to the resistant line; 18.8, 12.7, and 1.6% respectively (P < 0.001). Susceptible and relaxed lines showed more right ventricular hypertrophy when compared with the resistant line (P < 0.05). The results show that under severe cold stress at local altitude (390 m above sea level), the ascites-resistant line was growing as rapidly as the other lines and was as resistant to ascites as it had been under hypobaric conditions.

Photosynthetic responses of the coral Montipora digitata to cold temperature stress

Coral bleaching events have become more frequent and widespread, largely due to elevated sea surface temperatures. Global climate change could lead to increased variability of sea surface temperatures, through influences on climate systems, e.g. El Nino Southern Oscillation (ENSO). Field observations in 1999, following a strong ENSO, revealed that corals bleached in winter after unusually cold weather. To explore the basis for these observations, the photosynthetic responses of the coral species Montipora digitata Studer were investigated in a series of temperature and light experiments. Small replicate coral colonies were exposed to ecologically relevant lower temperatures for varying durations and under light regimes that ranged from darkness to full sunlight. Photosynthetic efficiency was analyzed using a pulse amplitude modulated (PAM) fluorometer (F-0, F-m, F-v/F-m), and chlorophyll a (chl a) content and symbiotic dinoflagellate density were analyzed with spectrophotometry and microscopy, respectively. Cold temperature stress had a negative impact on M digitata colonies indicated by decreased photosynthetic efficiency (F-v/F-m), loss of symbiotic dinoflagellates and changes in photosynthetic pigment concentrations. Corals in higher light regimes were more susceptible to cold temperature stress, Moderate cold stress resulted in photoacclimatory responses, but severe cold stress resulted in photodamage, bleaching and increased mortality. Responses to cold temperature stress of M digitata appeared similar to that observed in corals exposed to warmer than normal temperatures, suggesting a common mechanism. The results of this study suggest that corals and coral reefs may also be impacted by exposure to cold as well as warm temperature extremes as climate change occurs.

Thermoluminescence Investigation of Low Temperature Stress in Maize

The thermoluminescence (TL) emission of photosynthesising materials originates from the recombination of charge pairs created by a previous excitation. Using a recently described TL set-up the effect of chilling stress on TL bands occurring at positive temperatures (AG, B, and HTL) was investigated in intact leaves. The far-red irradiation of leaves at low, but non-freezing temperatures induced a TL band peaking at around 40–45 °C (AG band), together with a B band peaking between 20 and 35 °C. Low temperature stress first caused a downshift and a temporary increase in the AG band after 4 h at 0 °C in the light, then a decrease in the AG and B TL bands after 1 d at 0 °C in the light. This decrease was less pronounced in cold-tolerant genotypes and in those grown at acclimating temperatures. Furthermore, an additional band appeared above 80 °C after severe cold stress. This band indicates the presence of lipid peroxides. Thus TL is a useful technique for studying the effects of low temperature stress.

Basal metabolic adaptation of the Evenki reindeer herders of Central Siberia.

Previous research has suggested that basal metabolic rates (BMRs of indigenous circumpolar populations are elevated, perhaps as an adaptation to chronic, severe cold stress. This study examines variation in BMR among indigenous (Evenki) and nonindigenous (Russian immigrant) populations living in Central Siberia to determine: 1) whether the Evenki show evidence of increased metabolic rates, and 2) whether the metabolic responses of the Evenki are different from those of the recent Russian migrants ("controls"). BMRs were measured among 58 Evenki (19 men, 39 women) and 24 Russian (8 men, 16 women) adults (18-56 years of age) from three Siberian villages. Measured BMRs were compared to those predicted based on body weight and body SA (Consolazio et al., 1963; Schofield, 1985a,b). BMRs per unit weight and FFM were similar in Evenki and Russian men, whereas Evenki women had higher BMRs than their Russian peers. Relative to the Schofield (body weight) norms, Evenki men and women and Russian men all showed modest elevations in BMR, whereas Russian women had lower than expected BMRs. Compared to the Consolazio (surface area) estimates, both Evenki men and women showed significant elevations in BMR. Russian men also showed higher than expected BMRs, while those of Russian women were slightly below predicted levels. Age-related declines in BMR were evident among the women of both ethnic groups, but not among the men. Additionally, residence location was an important predictor of metabolic variation in the Evenki, with those of the more traditional village showing greater elevations in BMR. These results suggest that the Evenki display elevated metabolic needs, and this long-term adaptation reflects the interaction of genetics and level of acculturation. Am. J. Hum. Biol. 12:75-87, 2000. Copyright 2000 Wiley-Liss, Inc.

Cold adaptation and the seasonal distribution of acute myocardial infarction.

Numerous studies have reported an increased mortality from coronary heart disease (CHD) during the winter.1–,5 Observational epidemiological data in England and Wales have shown that mortality from cardiovascular disease (CVD) increases linearly with decrease in diurnal minimum from 17 °C, accounting for about half of all excess cold-related mortality,1,,2 which is approximately 50 000 per year in Britain alone.3 This effect is particularly pronounced in the elderly, in whom there is a 30% increase in deaths from this cause. Mortality increases more with a given fall of temperature in regions with `warm' winters.6 These deaths may therefore represent a graded effect of mild to severe environmental cold, rather than a specific effect of severe cold stress. The short temporal relation between temperature drop and mortality observed in Taiwan, where ambient temperature fluctuates greatly, supports the hypothesis that temperature effect may be a major factor which contributes to the increased mortality in winter.7 Increased CVD mortality has been related to thrombosis due to haemoconcentration in the cold.8,,9 Mortality from CVD increased significantly with short-term falls in temperature. Short term falls in temperature also significantly increase blood pressure, haemoglobin (Hb), erythrocyte count, packed cell volume and serum albumin—changes that persist for 1–2 days.10 The secondary effects of winter respiratory infections may contribute to CVD deaths as observed during influenza epidemics,11 probably because of increases in blood fibrinogen during infections.12 However, most of the coronary deaths occur some hours after the exposure to cold, and before respiratory deaths increase.13 There is also epidemiological evidence for an increased incidence of strokes during winter, however, the data regarding the increase in case-fatality rate are somewhat equivocal.14 The decline in seasonality of coronary mortality in the US since 1970 …

Response of shoal grass, Halodule wrightii, to extreme winter conditions in the Lower Laguna Madre, Texas

Effects of a severe freeze on the shoal grass, Halodule wrightii, were documented through analysis of temporal and spatial trends in below-ground biomass. The coincidence of the second lowest temperature (−10.6°C) in 107 years of record, 56 consecutive hours below freezing, high winds and extremely low water levels exposed the Laguna Madre, TX, to the most severe cold stress in over a century. H. wrightii tolerated this extreme freeze event. Annual pre- and post-freeze surveys indicated that below-ground biomass estimated from volume was unaffected by the freeze event. Nor was there any post-freeze change in biomass among intertidal sites directly exposed to freezing air temperatures relative to subtidal sites which remained submerged during the freezing period.

Food restriction and development of thermoregulation in Muscovy ducklings (Cairina moschata)

1. The interaction between the effects of food restriction and cold stress on the development of body temperature, homeothermy index, metabolic rate and body weight were studied in Muscovy ducklings from hatching to 21 d of age. 2. The control group (ad libitum fed) and the food restricted group (fed to zero growth rate for 9 d) both became homeothermic when they were 2 d old with moderate (10°C) cold stress. At severe cold stress (0°C) the control group was homeothermic 5 days after hatching. However the food restricted group did not reach homeothermy at 0°C and showed a large decrease (to hatching level) in homeothermy index at 10°C and 0°C after 9 d of food restriction. 3. Body temperature was lower in the food‐restricted group during restriction and increased by 1°C after 24 h of ad libitum feeding. During food restriction, resting metabolic rate did not increase with age and was lower than the basal and existence metabolic rate predicted by Aschoff and Pohl (1970) and Kendeigh (1970) respectively. 4. The ratio of metabolisable energy (ME) intake to resting metabolic rate was 3 times lower in the food‐restricted group than in the control group (0.09 and 0.27 respectively) on day 9. The availability of ME was more important than age for the development of thermoregulation in Muscovy ducklings. It is concluded that small improvements in the feeding regimen of young ducklings enhance the endurance and consequently reduce mortality from to environmental cold stress in a scavenger poultry system.

Winter Survival and Competition in a Mixture of Winter Wheat Cultivars

For winter wheat (Triticum aestivum L.) in western Canada, cold resistance is a major factor in winter survival ability (WSA) and yield stability. The few genotypes that display the highest levels of WSA are tall, low in yield potential and weak strawed. While improved types with good WSA have been developed, none of these are as hardy as the elite lines. This study examines the role of natural selection in the development of winterhardy wheats with desirable plant types. A mixture of six botanically distinguishable cultivars with wide differences in plant type and WSA was started from equal numbers of seed and grown repeatedly in southwestern Alberta over several environments and years. ‘Kharkov 22MC’, ‘Westmont’, ‘Jones Fife’, and ‘Gaines’ have all been cultivated commercially in southern Alberta while ‘Alabaskaja’ and ‘Bezostaya’ are also adapted. Under severe cold stress, tender cultivars killed out and winterhardy cultivars dominated the mixture in 1 yr. In a second experiment, six cycles of grain harvest and reseeding through milder winters produced similar changes (rs = 0.94, d.f. = 4, P &lt; 0.01) with no evidence of differential winterkill. For five cultivars, high reproduction in the second experiment was associated with the ability of pure stands to compete with adjacent rows (rs = 1.0, d.f. = 3, P &lt; 0.0001). The exception (Jones Fife) was tall and competitive as a pure stand but reproduced poorly in the mixture. Unlike most winter wheats which become prostrate in the fall, Jones Fife resembles spring wheat and keeps its leaves upright. Increased defoliation from freezing due to non‐prostrate plant habit may be expected to reduce the competitive ability of seedlings in mixtures during spring recovery. Jones Fife notwithstanding, tall and winterhardy cultivars with low yield survived best in the mixture while higher yielding, short‐strawed types survived poorly. In the absence of winterkill, changes hi the mixture were attributed to competition. To minimize the advantage of competitive types, mass selection for WSA should be conducted in high‐stress environments for a few generations only.

Seasonal Effects on Metabolism and Thermoregulation in Northern Bobwhite

Seasonal differences in metabolism and cold hardiness are common among small passerine birds. However, seasonal adjustments of metabolism and insulation are less well studied in nonpasserines and in larger birds. We measured basal metabolic rate (BMR), metabolic response to temperature, and maximal capacity for thermogenesis (peak cold-induced oxygen consumption, VO 2sum ) in late spring/summer and winter in outdoor captive Northern Bobwhite (Colinus virginianus) near the northern boundary of their natural range, to determine whether seasonal adjustments in metabolism are a component of acclimatization in this species. Mass, BMR and regression equations describing diurnal and nocturnal metabolic response to temperature were not significantly different between seasons. After metabolic tests below thermoneutrality, cloacal temperature (T b ) was not dependent on ambient temperature (T a ) at either season, and nocturnal T b did not differ significantly between seasons. However, after metabolic tests below thermoneutrality, diurnal T b was significantly greater in summer (38.9 ± 1.1°C) than in winter (37.7 ± 1.1°C). Although body mass of winter birds was significantly greater than their body mass in late spring, maximal thermogenic capacity did not differ significantly on a seasonal basis, and winter bobwhite were only marginally more cold tolerant than late spring birds under severe cold stress. For individual birds tested in both winter and late spring, individual ranking of VO 2sum was not consistent between seasons (i.e., birds with a high VO 2sum in winter did not necessarily have a high VO 2sum in late spring). These data suggest little seasonal adjustment of metabolism or insulation in the Northern Bobwhite, a relatively large nonpasserine species native mainly to regions with relatively mild winter climates.

Seasonal Acclimatization of Lipid Mobilization and Catabolism in House Finches (Carpodacus mexicanus)

Seasonal variation in cold tolerance is a well-documented form of winter acclimatization in birds. The physiological mechanisms of metabolic seasonal acclimatization, however, are not completely understood. This study of house finches (Carpodacus mexicanus) assessed the extent of seasonal changes in various parameters associated with lipid mobilization, including plasma levels of free fatty acids (FFA), albumin, and glucagon. Also, seasonal variation in the catabolic capacity of the pectoralis muscle was examined through the activities of key metabolic enzymes citrate synthase and β-hydroxyacyl-CoA dehydrogenase. Plasma FFA levels were seasonally stable in house finches exposed to moderate temperature. In birds exposed to severe cold stress, however, winter FFA values were significantly greater than those in late spring, suggesting a seasonal difference in lipid mobilization capacity. Mass-specific enzyme activities were seasonally stable, but greater pectoralis mass during winter resulted in increased total catabolic capacities in this muscle. Along with previous findings on body composition, these results provide evidence that adjustments in fat stores, ability to mobilize lipids, and catabolic capacity are all involved in metabolic seasonal acclimatization in house finches.

Body temperature rhythms and activity in reproductive Antechinus (Marsupialia)

To determine whether locomotor activity and body temperature (T b) rhythms change during the mating season of male Antechinus stuartii and whether that could contribute to postmating die-off, we measured both variables in individuals kept in the laboratory under natural photoperiod. Before the mating season Antechinus were mainly nocturnal. However, during the mating period (end of August) males showed a markedly elevated activity level and some animals extended their activity period well into the light phase. After about 2 weeks, normal activity patterns were restored. Activity was always accompanied by elevated T bs, whereas resting phases were characterized by low T bs. During the mating season the average daily T b was increased because animals maintained high T bs for longer time periods and because the resting T b was also elevated. The rise of both T b and locomotor activity during the mating season indicate an enhanced energy expenditure even when agonistic encounters between males and mating are excluded. However, under laboratory conditions without severe cold stress, food ad lib, and without social interaction males were able to avert postmating die-off.

Simple disturbance of the dam in the neonatal period can alter haloperidol-induced catalepsy in the adult offspring

Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood.

Chlorpromazine-induced alterations in hypothalamic amine metabolism and stress responses in severe cold

To investigate the effects on the central nervous system of severe cold stress with and without chlorpromazine, guinea pigs were treated with chlorpromazine or 0.9% NaCl and exposed to -20 degrees C or +23 degrees C for 1 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxy-tryptamine (5-HT), 3-methoxy-4-hydroxyphenyl ethylene glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum, urinary and vitreous fluid catecholamines, muscle and liver glycogen, and blood glucose were also measured. Chlorpromazine caused distinct hypothermia at -20 degrees C and slight hypothermia at +23 degrees C. The rise in hypothalamic MHPG, 5-HIAA and MHPG/NA and in 5-HIAA/5-HT ratios in the cold indicate increased noradrenergic and serotonergic activity. The latter was inhibited by chlorpromazine and a drug-induced inhibition of noradrenergic neurons could not be ruled out. Chlorpromazine increased the turnover of DA at room temperature and the same tendency was seen in the cold. The hypothermic animals had low serum catecholamines, indicating diminished sympathetic activity. The chlorpromazine-treated cold-exposed animals did not react to the environmental stress by sympathetic activation, as urinary NA and adrenaline were not elevated, but DA was excreted by all the drug-treated animals. Vitreous fluid NA and DA were elevated as an indicator of cold stress, and no drug effect was seen in this fluid.