Metabolic and thermoregulatory responses of the rat maintained in acrylic or wire-screen cages: Implications for pharmacological studies

doi:10.1016/0031-9384(94)90263-1

Physiology & Behavior

Volume 56, Issue 1, July 1994, Pages 73-79

https://doi.org/10.1016/0031-9384(94)90263-1 Get rights and content

Abstract

Because of differences in thermal conductivity, it is likely that a rodent's thermoregulatory requirements and their response to drugs and other stimuli will vary in metal and acrylic cages. To address these issues, thermoregulatory responses were measured in rats housed in an envirommental chamber with a floor made of either solid metal (aluminum) or acrylic materials (Plexiglas). Metabolic rate (M), evaporative water loss (E), thermal conductance (C), and tail skin (T_sk) and core temperature (T_c) were measured at ambient temperatures (T_a) of 10, 20, 28, 30, 32, and 34°C. These thermoregulatory variables were essentially unaffected by floor type at T_as of 20 and 28°C. The acrylic floor showed greater increases in M, E, T_c, and T_sk, but a smaller elevation in C as T_a increased from 28 to 34°C. At a T_a of 10°C, rats on the acrylic floor had a smaller M compared to that measured on the metal floor. Rats were then injected with saline or 30 mg/kg (SC) of 3,4-methylenedioxymethamphetamine (MDMA) and placed in an acrylic cage with wood chip bedding or a wire-screen cage at a T_a of 20°C. The MDMA caused T_c to increase > 2.0°C in rats in the acrylic cage but had no effect on T_c of rats in the wire-screen cage. The marked effect of cage type on basal thermoregulatory processes and thermogenic response to MDMA should be useful in the design and interpretation of many pharmacological studies.

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These data are the first to fully explicate the MDMA poikilothermic body temperature response (Malberg and Seiden, 1998; Dafters, 1994; Dafters, 1995) under intravenous self-administration conditions. A prior study (Gordon and Fogelson, 1994) showed that wire caging could block hyperthermia produced by 30 mg/kg s.c. in an acrylic cage. Thus, the predicted effect in operant boxes with metal flooring was for a decrease in body temperature even under 30 °C TA since this is still below normal rodent body temperature.
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High T_A appears to enhance acquisition of MDMA IVSA through an aversive effect and not via thermoregulatory motivation.
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Adult male rhesus monkeys were challenged intramuscularly (i.m.) and per os (p.o.) with 1.78 or 5 mg/kg (±)MDMA and with 0.1 or 0.32 mg/kg (+)METH. Temperature and activity were monitored with a radiotelemetry system.
Oral administration of either MDMA or METH produced significant increases in body temperature. Locomotor activity was suppressed by MDMA and increased by METH following either route of administration.
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Citation Excerpt :
When kept at room temperature in a cage with a metal floor that easily conducts heat away from the rat, the hyperthermic effects were less apparent. On a floor of low thermal conduction such as plastic or wood shavings, the hypothermic effects were most profound (Gordon and Fogelson, 1994). One of the most amazing effects on thermoregulation in the rat was the inability of the rat to vasodilate its tail in spite of encountering lethal hyperthermia (Fig. 5B).
This chapter focuses on the effects of hyperthermia on drug and chemical toxicity. In general, hyperthermia exacerbates the toxicity of many types of drugs and environmental toxicants. Using rodents to model the potential responses of humans to hyperthermic drugs is hampered by the unique differences in thermoregulatory ability and body mass. Because of their relatively large surface area:mass ratio, ambient temperature has a more profound influence on the potential hyperthermic effect of a drug in rodents. The relative increase in heat production (i.e., as a percentage of their basal metabolic rate) required to raise core temperature by 1°C will increase with a decrease in body mass. The thermoregulatory response to methylenedioxymethamphetamine (MDMA) is used to illustrate the differences in thermoregulatory responses of rats and humans to a hyperthermic drug. Overall, the interaction between ambient temperature and drug-induced changes in body temperature is critical in the evaluation of hyperthermic-induced toxicity in rodent models.
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Hyperthermia and hyperlocomotor activity are commonly reported acute effects of high dose, experimenter-delivered 3,4-methylenedioxymethamphetamine (MDMA). The current investigation was performed to determine short- to long-term physiological and behavioral changes induced by moderate intake MDMA self-administration. In the present study, rats self-administered MDMA (approx. 2.0–7.0 mg/kg/day) across 20 days during daily 2-h operant sessions. Locomotor activity was assessed during MDMA self-administration sessions and core temperatures were recorded before and after each session. Findings of the first several sessions showed core temperatures significantly decreased after MDMA self-administration compared to baseline and to a control group that self-administered saline during operant sessions. As sessions proceeded, the MDMA-induced hypothermic response diminished and core temperatures normalized, then increased during the last few sessions. Also, locomotor activity during MDMA self-administration sessions was initially equivalent to saline level activity, but increased by day 8 to significantly greater levels. Our findings demonstrate experience-dependent changes after voluntary administration of MDMA that are clearly observable in temperature regulation and behavioral activity.

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^☆: This paper has been reviewed by the Health Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

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ArticleMetabolic and thermoregulatory responses of the rat maintained in acrylic or wire-screen cages: Implications for pharmacological studies☆

Abstract

Toxicol. Appl. Pharmacol.

Physiol. Behav.

Pharmacol. Biochem. Behav.

Lancet

Brain Res.

Pharmacol. Biochem. Behav.

Influence of mild cold on the components of 24 hour thermogenesis in rats

J. Physiol.

Animal care and facilities

Article
Metabolic and thermoregulatory responses of the rat maintained in acrylic or wire-screen cages: Implications for pharmacological studies☆