In this study, we have examined the effects of estradiol and progesterone on pulsatile luteinizing hormone (LH) secretion in the rat. In the first experiment, regularly cycling rats were ovariectomized on metestrus and a Silastic implant containing estradiol in oil (7.5, 15 or 30 micrograms/ml) or crystalline progesterone (0.7 or 3 cm long) was placed s.c. immediately after surgery. Rats were cannulated 3 days later and frequent blood samples collected (every 10 min for 4 h) the next day. Estradiol treatment alone produced a dose-dependent suppression in mean LH by decreasing LH pulse amplitude without altering interpulse interval. Progesterone treatment alone had no effect, but when the low progesterone dose was combined with a subthreshold estradiol treatment, the combination decreased LH pulse amplitude, but had no effect on the interval between pulses. The combination of high progesterone and low estradiol completely suppressed LH secretion. In the second experiment, rats were bled 7 days postovariectomy to increase the postcastration LH rise and examine higher steroid treatments. Three progesterone treatments (0.7, 1.5 and 3 cm long implants) were combined with the low estradiol treatment; the high estradiol dose (30 micrograms/ml) was also tested. All treatments decreased LH pulse amplitude without altering interpulse interval, although the highest progesterone treatment again completely suppressed LH in most rats so that no statistical analysis could be performed. No firm conclusions can be drawn about the effects of the high steroid treatments that completely suppressed LH; such an effect could reflect either inhibition of pulse frequency or amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
The laboratory rat is being developed as a model to determine whether abuse of cocaine constitutes a risk factor in the pathogenesis of stress or exertion-induced heatstroke. Under thermoneutral conditions (Ta 20°C) cocaine (10–40 mg/kg i.p.) caused a dose-dependent fall in core temperature ranging from 0.45 ± 0.18 to 1.77 ± 0.26°C. When the ambient temperature (Ta) was increased to 35°C, cocaine (10–40 mg/kg i.p.) led to a dose-dependent hyperthermia (0.3 ± 0.08 to 1.43 ± 0.43°C). Repeated injection of cocaine (40 mg/kg at Ta 20°C or 20 mg/kg at Ta 40°C) on days 1, 3, 8, 15, and 23 did not alter the magnitude of the temperature change compared to that following the first injection, i.e., neither tolerance nor potentiation occurred.
The laboratory rat has been used as an animal model to investigate the effects of cocaine on body temperature and to determine if abuse of the drug is a risk factor in the pathogenesis of exercise-induced heat stroke. Animals were trained to run on a treadmill which was enclosed so that the ambient temperature could be regulated. Exercise at ambient temperatures of 20 and 30 °C led to a similar rise in core temperature of ≈1 °C, although the starting core temperature was higher in the rats at 30°C(38.5 ± 0.10 °C compared to 37.9 ± 0.06 °C). Cocaine (20 mg/kg) led to a transient fall in core temperature in the 20 °C group; the temperature then rapidly recovered, so that after 60 min exercise there was no significant difference between these and the control animals. At the higher ambient temperature cocaine augmented the rise in core temperature during running, although the animals had regained thermal balance by 30 min and core temperature was maintained at 40.2 ± 0.13 °C until the end of the exercise period. The dopamine D1 receptor antagonist SCH 23390 (0.1, 0.3 or 1.0 mg/kg) led to suppression of spontaneous motor activity so that the rats could be persuaded to exercise for only 30–45 min after treatment. Pretreatment with the antagonist did not affect the rise in core temperature induced by cocaine at 30 °C which again stabilized by 30 min at 40.0 ± 0.12 °C. It is concluded that toxic doses of cocaine can precipitate exercise-induced heat stroke at elevated ambient temperatures. Dopamine D1 antagonists would not seem to offer a useful therapeutic adjunct to the management of patients who develop hyperthermia after ingestion of cocaine; the first line of treatment should be directed at lowering body temperature by physical methods.
The laboratory rat is being used to determine if abuse of cocaine is a risk factor in the pathogenesis of exercise-induced heatstroke. The effect of running on a treadmill on the core temperature (Tc) has been studied in two groups of rats: animals ≈20 weeks old (‘young rats’) and animals « 52 weeks old (‘old rats’). During 60 min running the Tc increased to a steady level, within 15–30 min, which was higher in the old than in the young animals at environmental temperatures (Ta) of 25 and 30 °C. A significantly greater rise occurred in both groups of animals at Ta of 30 compared to 25 °C. Injection of cocaine (20 mg/kg) was without effect on the rise in Tc in young animals running at a Ta of 25 °C but significantly increased the hyperthermia in the old rats. It is suggested that the rise in the thermoregulatory set point induced by muscle exercise is greater with advancing age. Also in older animals, the effect of cocaine on the central nervous system may be enhanced.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.