Exposure of the fetus or newborn to ethanol (EtOH) can produce significant disturbances in normal growth and development. This may be due in part to a shift in basic physiological function. Mammalian homeostasis depends on mechanisms that regulate body temperature. Although the change in body temperature of adults following exposure to EtOH has been widely studied, little attention has been paid to the thermal and metabolic responses of immature animals. Initial tests indicate that the young rat exhibits a dose-dependent response to EtOH that varies with ambient temperature. The proposed study will determine, during a critical stage of development in the rat, specific alterations in the thermoregulatory ability that occur following a single injection of EtOH. At 2-17 days of age, a period of rapid brain growth and improvement in homeothermic ability, the rat is potentially vulnerable to systemic stressors such as EtOH. Physiological thermoregulatory responses (oxygen consumption, colonic and skin temperatures) of rats at 2-3, 8-9, and 14-15 days of age will be measured in a controlled thermoneutral environment to determine acute dose-responses to EtOH (1-4 g/kg BW; i.p.). Long-term tests will be performed following similar treatment with EtOH to detect changes in development of thermoregulatory ability which evolve from the initial hypothermic response. Experiments conducted at different ambient temperatures will assess how EtOH alters both thermogenic and thermolytic processes (e.g., rate and magnitude of response). The final stage of the study will examine the role of the beta-adrenergic system, extremely active in the young mammal, in the mediation of certain theramoregulatory responses to acute EtOH treatment. The primary aims of the work proposed are to determine if immature and adult animals respond similarly to EtOH and, also to derive certain generalizations regarding thermoregulatory response to this drug. In addition, the derived profile of early thermoregulatory response EtOH will be correlated with specific age-related changes in heat production and heat loss. The results of this study will provide a more thorough understanding of the action of EtOH on the developing organism and aid in predicting those responses to EtOH (e.g., growth rate, activity level) which depend on the functional integrity of the thermoregulatory system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA007845-01
Application #
3111792
Study Section
Alcohol Biomedical Research Review Committee (ALCB)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
John B. Pierce Laboratory, Inc.
Department
Type
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06519
Spiers, D E; Kelleher, S A; Eichen, P A (1996) Ethanol effect on activation and maintenance of cold stress response in immature rats. Pharmacol Biochem Behav 54:555-64
Spiers, D E; Fusco, L E (1992) Delayed thermoregulatory changes in the immature rat following a single injection of ethanol. Alcohol Clin Exp Res 16:41-7
Spiers, D E; Fusco, L E (1991) Age-dependent differences in the thermoregulatory response of the immature rat to ethanol. Alcohol Clin Exp Res 15:23-8