Effects of fetal alcohol exposure on fever, sickness behavior, and pituitary-adrenal activation induced by interleukin-1 beta in young adult rats.
Exposure to alcohol in utero can lead to long-lasting impairments of immune functions and to decreased resistance to infectious agents. We have previously reported that fetal alcohol-exposed rats show markedly decreased lipopolysaccharide-induced fever and suggested that fetal alcohol exposure (FAE) impairs the communication between the immune and the nervous systems. The present study examined the effects of interleukin-1 beta (IL-1) on body temperature, motor activity, ingestive behavior, and pituitary-adrenal activation in fetal alcohol-exposed and control rats. Transmitters for continuous biotelemetric recording of body temperature and motor activity were implanted i.p. in normal (N) adult rats, offspring of dams fed a liquid diet supplemented with ethanol (E), and pair-fed control offspring (P). In one experiment, rats were injected with either IL-1 (2 micrograms/kg, i.p.) or saline at the beginning of the light period. IL-1 produced a marked increase in body temperature, which was significantly lower in E rats than in N and P rats. In a second experiment, rats were administered either IL-1 (10 micrograms/kg, i.p.) or saline at the beginning of the dark period. IL-1 produced an initial transient hypothermia followed by a longer-lasting hyperthermia. During the hyperthermic phase, fever in the E rats was lower than in the P rats, but comparable to fever in the N rats. IL-1 significantly reduced motor activity, during both the hypothermic and hyperthermic phases. This effect was similar in all prenatal treatment groups. IL-1 also suppressed 24-h food consumption in N and P rats and water consumption in P rats, but it did not produce significant anorexia and adypsia in E rats. A third experiment demonstrated that IL-1 (2 micrograms/ kg, ip) significantly increased ACTH and corticosterone release in all prenatal treatment groups. IL-1-induced corticosterone secretion was attenuated in P offspring, compared to both E and N rats. Together, these findings indicate that exposure to ethanol in utero produces impairments in mechanisms that mediate the effects of IL-1 on body temperature (particularly during the light period) and ingestive behavior, but not on motor activity and pituitary-adrenal activation. In view of the adaptive role of IL-1-induced fever and anorexia, these impairments may contribute to the decreased resistance to infections observed in animals and humans following FAE.
Yirmiya
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Department of Psychology, Hebrew University of Jerusalem, Mount Scopus, Israel.
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Taylor
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D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology* / Q000523:psychology*; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017440:Photoperiod; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013686:Telemetry
D007375:Interleukin-1; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone