Cyrilla H. Wideman

Implications of an animal model of sugar addiction, withdrawal and relapse for human health

Abstract The effect of intermittent glucose administration on the circadian rhythm of body temperature was studied in rats to provide evidence of sugar addiction, withdrawal and relapse. Metabolic and behavioral phenomena were also observed. Biotelemetry transmitters recorded body temperature for the duration of the 4-week experiment. Rats were divided into an experimental and a control group, which were maintained on the same habituation conditions for the duration of the experiment, with the exception of weeks 2 and 4, when the experimental group was presented with a 25% glucose solution. Experimental animals displayed a precipitous drop in body temperature and behavioral changes associated with withdrawal during week 3, when sugar was removed. There was an increase in kilocalories (kcal) consumed during weeks 2 and 4 by experimental animals and, by the end of the experiment, these animals showed a greater percent increase in body weight. Elevated blood glucose levels were found in experimental animals. The study demonstrates that the effects of sugar addiction, withdrawal and relapse are similar to those of drugs of abuse. Implications of the rewarding and addicting effects of sugar are related to weight gain, obesity and Type II diabetes. Furthermore, pitfalls related to dieting are elucidated.

Constant light induces alterations in melatonin levels, food intake, feed efficiency, visceral adiposity, and circadian rhythms in rats

Abstract Melatonin levels, metabolic parameters, circadian rhythm activity patterns, and behavior were observed in rats subjected to a 12-h/12-h light/dark cycle (LD) compared to animals exposed to continuous dark (DD) or continuous light (LL). LD and DD animals were similar in melatonin levels, food intake, relative food intake, feed efficiency, water intake, circadian activity levels, and behavior. LL animals had lower melatonin levels in the subjective dark compared to LD and DD animals. Food intake, relative food intake, and water intake values were lower and feed efficiency was more positive in LL animals compared to LD and DD animals. In addition, LL animals exhibited greater visceral adiposity than the other two groups. The circadian rhythmicity of activity became free-running in LL animals and there was a decrease in overall activity. Notable behavioral changes in LL animals were an increase in irritability and excitability. Results indicate that a decrease in melatonin levels and concomitant changes in metabolism, circadian rhythms, and behavior are consequences of exposure to constant light.

Plasma Corticosterone Levels and Ulcer Formation in Rats with Hippocampal Lesions

In order to examine the effects of hippocampal lesions on plasma corticosterone levels and ulcer formation, 4 conditions were studied: (1) unrestrained nondeprived (2) unrestrained 24 h food-deprived (3) simple restraint and (4) restraint plus intermittent shock. In the unrestrained and unrestrained plus 24 h food-deprived conditions, neither animals with hippocampal lesions nor control animals developed ulcers. In both instances plasma corticosterone levels were similar in experimental and control animals. Differences appeared in the simple restraint and restraint plus intermittent shock conditions. In both of these conditions animals with hippocampal lesions developed more ulcers and had a higher corticosterone level than controls. It is concluded that animals with hippocampal lesions show an enhanced reaction to stress.

The interaction of vasopressin and the photic oscillator in circadian rhythms.

Telemetered body temperature (BT), heart rate (HR), and activity (AC) data were collected in vasopressin-containing Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. The rats were exposed to a 12/12 h light/dark cycle under three conditions: 1) ad lib feeding throughout the 24-h cycle, 2) two scheduled-feeding periods during the diurnal component of the light/dark cycle, and 3) two scheduled-feeding periods during the nocturnal component of the light/dark cycle. With ad lib feeding, natural nocturnal cycles of BT, HR, and AC were maintained in both strains. Marked changes were observed under the condition of scheduled feeding during the diurnal component of the light/dark cycle. In DI animals the influence of the photic oscillator was lost and BT, HR, and AC shifted from nocturnal to diurnal patterns. Circadian rhythms in DI animals were now synchronized by the nonphotic zeitgeber of scheduled food presentation. On the other hand, LE animals lost a well-defined circadian rhythmicity resulting from adherence to the photic oscillator, while at the same time being influenced by the nonphotic oscillator. Under the condition of scheduled feeding during the nocturnal component of the light/dark cycle, the circadian rhythms were similar in DI and LE rats. Results show that vasopressin has a significant interaction with the photic oscillator, which is obvious only when the photic and nonphotic oscillators are uncoupled. In addition, the results demonstrate that the strength of the photic oscillator is decreased or that the effect of this oscillator is masked or lost in DI rats compared to LE rats.

Vasopressin, corticosterone levels, and gastric ulcers during food-restriction stress

Corticosterone levels and ulcers were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar corticosterone levels and no ulcers. After 1 day of food restriction, the corticosterone levels were elevated in DI and LE rats, with a significantly higher level in LE rats. No ulcers were present in either strain. After 2 days of food restriction, the corticosterone levels were similar in DI and LE rats. The level in DI rats was comparable to that of the preceding day, but the level in LE animals dropped significantly from the previous day. Significant ulceration was evident in DI rats, but absent in LE rats. Following 3 days of food restriction, the corticosterone level in LE rats had returned to the ad lib level, whereas, for DI rats, an elevated level was maintained. There were no ulcers in LE rats, but they were present in DI rats. Thus LE and DI rats responded differently to the stress of food restriction. The mechanism underlying the response is most likely related to changes in the hypothalamic-pituitary-adrenocortical axis and its reaction to stress.

Effects of vasopressin deficiency, age, and stress on stomach ulcer induction in rats.

Susceptibility to ulceration induced by restraint, restraint plus intermittent shock, and activity stress was studied in 6 week and 18 week old Brattleboro and Long-Evans rats. Older animals developed more glandular ulcers than younger animals with Brattleboro rats having significantly greater ulceration than Long-Evans rats in both conditions. With activity stress, younger subjects developed significantly more glandular ulcers than older subjects; whereas, older subjects developed significantly more nonglandular ulcers than younger subjects. In both instances, the ulceration was significantly greater in Brattleboro rats than in Long-Evans rats. There were significantly high correlations among running behavior, survival time, and the development of glandular ulcers in younger animals exposed to activity stress. The presence of vasopressin, as well as the age of the subject and the nature of the stress, influences the type and degree of stomach pathology induced.

Vasopressin deficiency and circadian rhythms during food-restriction stress

Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient, Brattleboro (DI) rats were monitored for activity and core body temperature via telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate with ad lib access to food and water. The habituation period was followed by an experimental period of 23 h of food-restriction stress in which a 1-h feeding period was provided during the light cycle. Although both strains of animals showed nocturnal activity and temperature rhythms during the habituation period, DI rats were more active than LE rats. The DI rats also had a lower body temperature in the dark. During the experimental period, both strains exhibited a phase shift of activity and body temperature correlating with the presentation of food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI animals showed a dramatic increase in activity during the light phase and a marked decrease in body temperature during the dark phase. The LE animals showed a significant attenuation of activity, but maintained both nocturnal and diurnal temperature peaks throughout the food-restricted condition.

The role of vasopressin in modulating circadian rhythm responses to phase shifts

Telemetered body temperature (BT), heart rate (HR), and motor activity (AC) data were collected in vasopressin-containing, Long-Evans (LE) and vasopressin-deficient, Brattleboro (DI) rats. In Experiment 1, the rats were initially exposed to a 12 h/12 h light/dark cycle under ad-libitum feeding and were then subjected to either a phase-advance or phase-delay shift of 6 h. After the phase-advance shift, neither strain adapted; however, after the phase-delay shift, both strains adapted rapidly. In Experiment 2, the animals were subjected to either a nocturnal or a diurnal restricted-feeding paradigm and were then exposed to either a phase-advance or phase-delay shift with synchronized feeding. In the nocturnal restricted-feeding paradigms, both strains rapidly adapted to both shifts. Concerning diurnal restricted-feeding, DI animals readily entrained to the presentation of food in both shifts; whereas, LE animals exhibited a confused rhythmicity. In Experiment 3, animals were subjected to a phase-advance shift, while the time of feeding was held constant. Following the shift, LE animals responded to the onset of the dark at the new time; yet, were still influenced by the presentation of food. The DI animals maintained the preshift circadian pattern and continued to be dominated by the presentation of food. These experiments indicate that circadian rhythms of LE animals are dominated by the light entrainable oscillator (LEO) in ad-libitum feeding and by both the LEO and food entrainable oscillator (FEO) in restricted-feeding. On the other hand, the circadian rhythms of DI animals are dominated by the FEO unless food is provided ad-libitum. The demonstrated role of vasopressin in synchronizing circadian rhythms to the LEO may be of significance in understanding human circadian rhythm disturbances, such as jet lag.

Modulatory effects of vasopressin on glucose and protein metabolism during food-restriction stress

Plasma levels of glucose and urea nitrogen were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar levels of glucose and urea nitrogen. Variations in this pattern were observed under food-restricted conditions. The DI animals exhibited lower levels of glucose and higher levels of urea nitrogen than their LE counterparts. During food restriction, the glucose levels of LE animals were not different from that observed under ad lib conditions. A significant decrease, however, was observed in the glucose levels in DI animals during food restriction. Urea nitrogen levels in LE animals decreased during food restriction as compared to the ad lib situation, whereas urea nitrogen levels of DI animals increased during food restriction. These observations indicate that vasopressin has a modulatory role on glucose and protein metabolism during the stress of food restriction.

Effects of vasopressin replacement during food-restriction stress

The effects of subcutaneous injections of vasopressin in vasopressin-deficient (Brattleboro or DI) rats were observed during nonstress (habituation) and stress (food-restriction) conditions as compared to other rats. Four groups of animals were employed: 1) Long-Evans (LE) rats that were food restricted with no injections (normal control animals), 2) DI rats that were food restricted with no injections, 3) DI rats injected with vasopressin, and 4) DI rats injected with peanut oil (vehicle). The parameters studied were: body weight, food intake, water intake, and gastric ulcer formation. With respect to body weight, water intake, and ulcer formation, two sets of animals emerged. The vasopressin-injected DI rats resembled the LE control rats, whereas the peanut oil-injected DI rats were similar to the DI rats with no injections. The former set of animals showed a higher body weight, reduced water intake, and fewer gastric ulcers than the latter set of animals. Thus the vasopressin-injected DI rats and the LE control rats could cope with the stress of food restriction, but the peanut oil-injected DI rats and the DI rats with no injections could not.