Cocaine and Body Temperature in the Rat: Effects of Ambient Temperature

Lomax, Peter; Daniel, Keri A.

doi:10.1159/000138648

Cited by 28 publications

(17 citation statements)

References 10 publications

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“…Factors such as species (mice vs rats), dose, route of administration, time of day, duration of temperature measurement, location of temperature measurement (core, peripheral, or IBAT), or ambient temperature could have influenced BUP's effects on temperature. Ambient temperature has been demonstrated to influence the effect of cocaine on body temperature (Lomax and Daniel, 1990). Similar to cocaine, BUP has little effect on temperature in humans in a thermoneutral environment, but may increase temperature in a warm environment due to a higher set point for hyperthermia and reduced compensatory heat loss (Griffith et al, 1983;Watson et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Billes

Cowley

2007

Neuropsychopharmacol

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Bupropion (BUP) is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor that causes mild weight loss in obese adults. Subchronic (7 day) coadministration of selective DA and NE reuptake inhibitors also causes weight loss in mice. Because weight loss was not associated with decreased caloric intake, subchronic BUP might cause weight loss through increased energy expenditure. Acute studies demonstrate that BUP or DA + NE reuptake inhibitors cause transient hypophagia and increased locomotion; though the effects on temperature are inconsistent. Because subchronic DA + NE reuptake inhibition does not affect appetite, there is clearly a difference between the acute and subchronic effects of DA + NE reuptake inhibitors; however the effects of chronic (or subchronic) BUP on energy balance have never been directly studied in an animal model. Therefore, the acute and subchronic effects of BUP or selective DA and NE reuptake inhibitors on food intake, body weight, locomotor activity, and interscapular temperature were determined in mice. Generally, selective inhibition of DA reuptake (by GBR12783) increased activity while selective inhibition of NE reuptake (by nisoxetine, NIS) decreased activity and temperature. BUP increased activity and temperature but subchronic BUP did not significantly reduce body weight due to a compensatory increase in food intake. Subchronic DA + NE reuptake inhibitor coadministration mimicked the effect of BUP on activity and temperature, but caused weight loss because daily food intake was not increased. The results of this study suggest that the mild weight loss effect of BUP in humans may be due to increased locomotion or heat production. More importantly, inhibition of DA + NE reuptake (with GBR + NIS) increased energy expenditure without a compensatory increase in food intake, supporting a role for novel combination catecholamine reuptake inhibitors in pharmacotherapy for obesity.

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Section: Discussionmentioning

confidence: 99%

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Billes

Cowley

2007

Neuropsychopharmacol

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“…I n earlier studies in the rat [ 12] cocaine (10-40 mg/kg) caused a dose-dependent fall in Tc under thermoneutral (20 °C) ambient condi tions and a dose-dependent rise at Ta 35 °C. During running at Ta 22 °C a delayed (30-45 min after injection) rise in Tc, compared to controls, occurred after a dose of 30 mg/kg: cocaine (10-20 mg/kg) was without effect [ 13], Pretreatment with SCH 23390 did not af fect the magnitude of cocaine hypothermia but delayed the recovery of Tc at Ta 20 °C.…”

Section: Discussionmentioning

confidence: 94%

“…Injection of co caine (10-40 mg/kg (into the rat causes a dose-dependent change in core temperature (Tc) which is a function of the ambient tem perature (Ta) [11,12], At normal laboratory temperatures (Ta 22 °C) a fall in Tc occurs which is accompanied by vasodilation in the tail during the early period when the tempera ture is falling (suggesting a downward shift of the thermoregulatory set point). When Ta is above 30 °C administration of cocaine leads to hyperthermia.…”

Section: Introductionmentioning

confidence: 99%

Cocaine and Body Temperature: Effect of Exercise at High Ambient Temperature

Lomax¹,

Daniel²

1993

Pharmacology

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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.

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“…In rats trained to run on a treadmill a rise in Tc occurs at normal Ta (22 °C). Under the same conditions the ad ministration of cocaine (30 mg/kg) causes hyperthermia which is significantly greater than that observed in vehicle-injected con trols [6], When the injections of cocaine were repeated at intervals of 1-23 days [6] or at recurring 7-day periods [7], the temperature changes were of the same magnitude, i.e. nei ther tolerance nor potentiation were in evi dence.…”

Section: Introductionmentioning

confidence: 82%

“…These studies have dem onstrated that cocaine causes a dose-depen-dent rise in body temperature when the Ta is above 30 °C [5,6]. In rats trained to run on a treadmill a rise in Tc occurs at normal Ta (22 °C).…”

Section: Introductionmentioning

confidence: 99%

Cocaine and Body Temperature in the Rat: Effects of Exercise and Age

Lomax¹,

Daniel²

1990

Pharmacology

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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 (T_c) 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 T_cincreased to a steady level, within 15–30 min, which was higher in the old than in the young animals at environmental temperatures (T_a) of 25 and 30 °C. A significantly greater rise occurred in both groups of animals at T_a of 30 compared to 25 °C. Injection of cocaine (20 mg/kg) was without effect on the rise in T_c in young animals running at a T_a 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.

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Cocaine and Body Temperature in the Rat: Effects of Ambient Temperature

Cited by 28 publications

References 10 publications

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Cocaine and Body Temperature: Effect of Exercise at High Ambient Temperature

Cocaine and Body Temperature in the Rat: Effects of Exercise and Age

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