Prenatal exposure to nicotine attenuates stress-induced hyperthermia in 7- to 8-week-old rats upon exposure to a novel environment.

Given that approximately 25% of women in the United States continue to smoke cigarettes during pregnancy, it is important to know if exposure to nicotine during development alters the physiological response of the adult to the "stressors" of everyday life. Our current experiments were carried out to determine if prenatal exposure to nicotine alters "stress-induced hyperthermia" in adult rats upon exposure to a novel environment such as a simulated open field. Forty-eight rats (23 males and 25 females) were exposed to a simulated open field or left in their home cage at 7 to 8 weeks of postnatal life (i.e., adulthood as defined by the ability to reproduce) following prenatal exposure to vehicle or nicotine (6 mg of nicotine tartrate per kilogram of maternal body weight per day) via a maternally implanted osmotic minipump from Day 6 or 7 of gestation. The simulated open field consisted of a 30(W)x60(L)x24(H)-in. white acrylic finish box illuminated by two hanging fluorescent lights and core temperature was measured by telemetry. Exposure to a simulated open field following prenatal exposure to vehicle elicited an increase in core temperature in male and female rats with a magnitude of approximately 1.2 degrees C and a duration of greater than 170 min. Prenatal exposure to nicotine significantly attenuated the thermogenic response of both genders; this was not only evident in the latency, magnitude and duration of the core temperature response but also in the core temperature index determined from the 3-h period following exposure to a simulated open field. Thus, our data provide evidence that prenatal exposure to nicotine attenuates stress-induced hyperthermia in male and female 7- to 8-week-old rats upon exposure to a "stressor" of everyday life (i.e., a novel environment).

Role of AVP in mediating the altered core temperature response to a simulated open field in pregnant rats.

Near the term of pregnancy, rats have an attenuated core temperature response on exposure to a novel environment (e.g., a simulated open field) compared with that observed early in pregnancy or in nonpregnant rats. The present experiments were carried out on 26 nonpregnant and 26 pregnant rats to test the hypothesis that arginine vasopressin, functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated core temperature response. Exposure to a simulated open field after intracerebroventricular (ICV) vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which were greater in the nonpregnant rats. In nonpregnant rats, exposure to a simulated open field after ICV vasopressin V(1)-receptor antagonist altered the pattern of the core temperature response but not the core temperature index compared with that observed on exposure to a simulated open field after ICV vehicle. In pregnant animals, ICV vasopressin V(1)-receptor antagonist did not alter the core temperature response to a simulated open field compared with that observed after ICV vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin attenuates the core temperature response to a simulated open field in rats near the term of pregnancy.

Arginine vasopressin does not mediate the attenuated febrile response to intravenous IL-1beta in pregnant rats.

Rats have an attenuated febrile response to intravenous endogenous pyrogen [e.g., interleukin-1beta (IL-1beta)] near the term of pregnancy. The present experiments were carried out on 25 nonpregnant and 32 pregnant rats to test the hypothesis that arginine vasopressin functioning as an endogenous antipyretic substance in the central nervous system mediates this attenuated febrile response. An intravenous injection of recombinant rat IL-1beta (rrIL-1beta) after intracerebroventricular vehicle produced a significant increase in core temperature in both nonpregnant and pregnant animals, the magnitude and duration of which was greater in the nonpregnant rats. In nonpregnant rats, intravenous rrIL-1beta after intracerebroventricular vasopressin V1-receptor antagonist accentuated the core temperature response compared with that observed with intravenous rrIL-1beta after intracerebroventricular vehicle. In pregnant animals, however, intravenous rrIL-1beta after intracerebroventricular vasopressin V1-receptor antagonist produced a decrease in core temperature rather than an increase in core temperature, which was observed with intravenous rrIL-1beta after intracerebroventricular vehicle. Thus our data do not support the hypothesis that a pregnancy-related activation of arginine vasopressin as an endogenous antipyretic substance in the central nervous system attenuates the febrile response to intravenous rrIL-1beta near the term of pregnancy in rats.

AVP mediates the attenuated febrile response to administration of PGE1 in rats near term of pregnancy.

Rats have an attenuated febrile response to intracerebroventricular injection of PGE1 near the term of pregnancy, the mechanism of which is unknown. The present experiments were carried out to test the hypothesis that arginine vasopressin (AVP), functioning as an endogenous antipyretic substance in the central nervous system, mediates this attenuated febrile response. The febrile response to intracerebroventricular injection of 0.2 microg PGE1 was determined in pregnant and nonpregnant rats after an intracerebroventricular injection of either vehicle or a vasopressin V1-receptor antagonist. After intracerebroventricular administration of vehicle, intracerebroventricular administration of 0.2 microg PGE1 produced significant increases in core temperature in both nonpregnant and pregnant animals. The increase in core temperature, however, was attenuated both in magnitude and duration in pregnant compared with nonpregnant animals. After intracerebroventricular administration of a vasopressin V1-receptor antagonist, intracerebroventricular administration of 0.2 microg PGE1 produced significant increases in core temperature that were similar in nonpregnant and pregnant animals. Our data support the hypothesis that a pregnancy-related activation of AVP as an endogenous antipyretic substance in the central nervous system attenuates the febrile response to intracerebroventricular administration of PGE1 near term of pregnancy in rats.

Autonomic and behavioral thermoregulation in guinea pigs during postnatal maturation.

Serial experiments were carried out on seven chronically instrumented Hartley-strain guinea pigs at 1, 3, and 5 wk of age to define their autonomic and behavioral thermoregulatory profiles and to test the hypothesis that they have the mechanisms in place shortly after birth that allow them to optimize their energy expenditure for thermoregulation by selecting a thermal environment that requires the lowest metabolic oxygen requirements. Each animal was studied in both a thermocline to determine selected ambient temperature and in a metabolic chamber to determine the thermoregulatory response to forced changes in ambient temperature. In the thermocline, the guinea pigs at all postnatal ages selected an ambient temperature that placed core temperature, oxygen consumption, thermal conductance, heart rate, and respiratory rate at levels comparable to those observed at ambient temperatures in which minimal oxygen consumption occurred in the metabolic chamber. Thus our experiments provide evidence that guinea pigs have the neurophysiological mechanisms in place shortly after birth that allow them to optimize their energy expenditure for thermoregulation by selecting a thermal environment that corresponds to the lowest metabolic oxygen requirements.

Thermoregulatory control during pregnancy and lactation in rats.

Although the mechanisms remain unknown, maternal core temperature (Tc) decreases near term of pregnancy and is increased throughout lactation in rats. The purpose of our present experiments was to determine whether pregnancy and lactation shift the thermoneutral zone of rats and to investigate whether the changes in maternal Tc during pregnancy and lactation result from "forced" or "regulated" thermoregulatory responses. Conscious, chronically instrumented nonpregnant and pregnant and lactating rats were studied both in a thermocline (a chamber with a linear temperature gradient from 12 to 36 degrees C) and in a metabolic chamber to determine the influence of pregnancy and lactation on selected ambient temperature as well as the thermoregulatory response to changes in ambient temperature. We found that selected ambient temperature, oxygen consumption, and thermal conductance did not change in rats studied in a thermocline as Tc decreased near term of pregnancy. There was, however, a downward shift in the thermoneutral zone of rats studied in a metabolic chamber near term of pregnancy. During lactation, selected ambient temperature decreased in rats studied in a thermocline as oxygen consumption and Tc increased. The thermoneutral zone of lactating rats was not different from that of nonpregnant animals. Thus our data provide evidence that the decrease in Tc near term of pregnancy in rats results from a regulated thermoregulatory response, whereas the increase in Tc during lactation results from a forced thermoregulatory response.

Influence of pregnancy on the febrile response to ICV administration of PGE1 in rats studied in a thermocline.

Rats near term of pregnancy have an attenuated febrile response to intracerebroventricular (ICV) injection of prostaglandin E1 (PGE1) when they are studied at an ambient temperature below their thermoneutral zone. Given that nonshivering thermogenesis in brown adipose tissue is impaired in rodents near term of pregnancy, it is possible that the attenuated febrile response is forced by impairment of this component of the autonomic thermoregulatory response. If this were the case, then near-term pregnant rats should develop a "normal" fever after PGE1 administration if they were studied in a thermocline where they could utilize behavioral as well as autonomic thermoregulatory effectors to increase their body core temperature (Tbc). Experiments were, therefore, carried out on 13 nonpregnant and 14 pregnant chronically instrumented rats in a thermocline (temperature gradient 10-40 degrees C) to investigate their Tbc responses to ICV injection of PGE1. ICV injection of 0.2 microgram PGE1 produced significant increases in Tbc and fever index in both nonpregnant and pregnant animals (day 19 of gestation); the increases, however, were significantly attenuated in the pregnant compared with the nonpregnant rats. Behavioral (e.g., selected ambient temperature) and autonomic (e.g., oxygen consumption) thermoregulatory effectors were activated to increase Tbc after ICV PGE1 in both groups of animals, but the duration of activation was shortened in pregnant compared with nonpregnant rats. The abbreviated thermoregulatory effector responses and the resulting attenuated febrile response to PGE1 in the pregnant rats may have resulted from a pregnancy-related activation of an endogenous antipyretic system.