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Biomedical subjects

H M Murphy

Publications and source records attributed to H M Murphy.

At least 19 recordsLinked to original sources

Vasopressin deficiency provides evidence for separate circadian oscillators of activity and temperature.

Vasopressin-containing Long-Evans and vasopressin-deficient Brattleboro rats were maintained in individual cages while telemetered activity (AC) and body temperature (BT) data were collected. Rats were initially exposed to a 12 h/12-h light/dark cycle (photic zeitgeber) and were allowed ad-libitum access to food and water. Daily feeding, care, and handling (nonphotic zeitgebers) occurred at the beginning of the second hour of the dark cycle. After a 14-day habituation period, rats were subjected to continuous light (LL) or dark (DD) and nonphotic cues were presented irregularly. During the habituation period, both strains exhibited clear 24-h circadian rhythms of AC and BT. In LL or DD, photic cues were removed and nonphotic cues were presented irregularly. There was a shift in the rhythm for Long-Evans animals to 26 h for both AC and BT in LL and 24.6 h in DD. Feeding, care, and handling were seen as minor artifact. In Brattleboro rats, although there were robust 26-h and 24.6-h circadian rhythms of AC in the LL and DD, respectively, BT data were inconsistent and showed sporadic fluctuations. In the BT rhythm of Brattleboro animals, strong peaks were associated with feeding, care, and handling times and trough periods were characterized by a dramatic drop in temperature. This experiment demonstrates that AC and BT are controlled by separate oscillators. In addition, the importance of vasopressinergic fibers in the control of circadian rhythms of BT is evidenced by the loss of circadian rhythms in animals lacking these functional fibers when exposed to free-running paradigms where there is no entrainment of photic or nonphotic oscillators.

Animals↗

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.

Animals↗

Role of vasopressin in long-term preferences of sucrose and polycose under ad-libitum and food-restricted conditions.

Vasopressin-deficient (DI) and vasopressin-containing (LE) rats were given continuous access to 32% sucrose and 32% polycose solutions under ad-libitum and food-restricted conditions in a long-term preference test. Although all animals preferred Polycose to sucrose in both conditions, food restriction introduced a stress that significantly increased the consumption of Polycose in DI rats. Considering total caloric intake, Polycose was preferred by both strains only under food restriction and the effect was greatly exacerbated in DI animals compared to LE animals. The differences observed between DI and LE animals in response to ad-libitum feeding and food-restriction stress indicate that vasopressin, directly and/or indirectly, influences the physical and metabolic functions and processes of the animals, which, in turn, affect their intake of Polycose.

Animals↗

Interactions between vasopressin and food restriction on stress-induced analgesia.

To investigate the role of the hormone vasopressin (VP) in mediating the response of an organism to food restriction stress-induced analgesia, tail flick latencies and scored qualitative behavioral responses were recorded in VP-containing (LE) rats and VP-deficient (DI) rats. These variables were measured under nonstressed (ad lib) and stressed (food restriction) conditions. In the ad lib condition, DI and LE rats had a similar tail flick latency and scored qualitative behavioral response to the stimulus eliciting the tail flick. During the food restriction condition, however, LE animals developed significant food restriction stress-induced analgesia, as measured by tail flick latency. On the other hand, DI animals did not develop significant analgesia. In addition, DI animals exhibited a significantly greater scored qualitative behavioral response to the stimulus eliciting the tail flick than LE animals. These results demonstrate that VP plays an important role in the regulation of food restriction stress-induced analgesia, as well as the scored qualitative behavioral response elicited by the tail flick stimulus.

Analgesia↗

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.

Animal Nutritional Physiological Phenomena↗

Vasopressin, immobilization, and the dexamethasone suppression test in rats.

To investigate the role of the hormone vasopressin (VP) in mediating the response of the body to stress, corticosterone levels of VP-containing (LE) rats and VP-deficient (DI) rats were compared following administration of the dexamethasone suppression test (DST) under stressed and nonstressed conditions. The stressor utilized was immobilization, an acute physical stressor. Dexamethasone (DEX), a synthetic glucocorticoid, was injected subcutaneously at a dose of 0.025 mg/kg. This dose of DEX was found to significantly suppress plasma corticosterone in the nonstressed animals (both DI and LE) via feedback inhibition of the hypothalamic-pituitary-adrenocortical (HPA) axis. In the stressed situation, however, LE animals exhibited "escape" from DEX suppression, whereas DI animals did not. Escape indicates a resistance of the HPA axis to the suppressive action of DEX. Thus, in the absence of corticotropin-releasing factor, which is inhibited by DEX, VP alone appears to be sufficient to elicit significant corticosterone release. These results support the hypothesis that VP plays an important role in the regulation of glucocorticoid release in acute stress via the HPA axis.

Animals↗

Vasopressin deficiency and blood glucose interactions on passive avoidance behavior.

The performance of a passive avoidance task (measured for two trials based upon number of complete step-downs and latency to respond) and blood glucose levels were examined in five groups of animals. The groups included vasopressin-deficient (DI) and vasopressin-containing (LE) rats under ad lib (AL) and food-restricted (FR) conditions, as well as DI-FR animals provided with access to an 8% sucrose solution (SUC). In the AL condition, no significant differences were found between DI and LE animals in either step-down occurrences or blood glucose levels. However, the DI animals were significantly slower in latency to respond in trial 1. With FR, the LE animals resembled the LE-AL animals in both passive avoidance behavior and blood glucose levels. The DI-FR animals that were not provided with SUC showed an impairment in passive avoidance behavior and low blood glucose levels, whereas DI-FR animals provided with SUC showed an amelioration of passive avoidance deficiencies and had blood glucose levels comparable to AL animals and LE-FR animals. On trial 2, a significant negative correlation was found between number of step-down occurrences and blood glucose levels, and a significant positive correlation was found between latency to respond and blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

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.

Aging↗

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.

Animals↗