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C J Gordon

Publications and source records attributed to C J Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1994

Autonomic and behavioral thermoregulation in the golden hamster during subchronic administration of clorgyline.

Chronic administration of clorgyline, a type-A monoamine oxidase inhibitor, leads to a decrease in peritoneal (i.e., core) temperature of golden hamsters. To better understand the mechanisms of clorgyline's thermoregulatory effects, autonomic and behavioral thermoregulatory effectors were measured in Syrian hamsters following chronic infusion of clorgyline via a minipump (2 mg/kg/day). Metabolic rate, evaporative water loss, motor activity, and core temperature were measured after 60 min of exposure to ambient temperatures (Ta) of 5, 20, 30, and 35 degrees C. Behavioral thermoregulatory responses were assessed by measuring selected Ta and motor activity of the same animals in a temperature gradient over the course of 23 h. Metabolic rate and motor activity were significantly elevated in clorgyline-treated hamsters exposed to a Ta of 5 degrees C. There were no effects of clorgyline on evaporative water loss. In the temperature gradient the mean selected Ta of clorgyline-treated hamsters was nearly equal to that of the saline-treated hamsters, 30.7 and 31.2 degrees C, respectively. On the other hand, the mode of selected Ta in the clorgyline group was 2.8 degrees C higher than that of the saline group. Motor activity in the gradient was significantly elevated and food consumption was depressed by clorgyline treatment. Overall, these findings indicate that chronic clorgyline treatment in the golden hamster results in novel autonomic and behavioral modification; it stimulates metabolic thermogenesis during cold exposure, but appears to increase the behavioral zone of thermoneutrality. This latter effect may mean an improvement in heat tolerance, suggesting that this drug might assist in the adaptation to warm temperatures.

Animals↗
PubMed1994

24-hour control of body temperature in rats. I. Integration of behavioral and autonomic effectors.

Some studies suggest that the nocturnal elevation in core temperature (Tc) of the rat is mediated by an elevation in the set point. The role of set point can be assessed if behavioral effectors are measured simultaneously with other thermoregulatory effectors and Tc over a 24-h period. Selected ambient temperature (STa) and motor activity (MA) were measured in rats housed in a temperature gradient system with a 12:12-h photoperiod (lights on 0600 h). Tc and heart rate (HR) were monitored by telemetry. During the light phase, STa, Tc, HR, and MA were relatively stable with values 29.0 degrees C, 37.1 degrees C, 310 beats/min, and 1-2 m/h, respectively. During the light-to-dark transition there were abrupt elevations in Tc, HR, and MA but no change in STa. STa decreased during the dark phase and reached a nadir of 23 degrees C at 0500 h. All variables recovered to basal levels within 3-4 h after the onset of the light phase. Overall, autonomic effectors control the elevation in Tc during the onset of the dark phase while behavioral effectors have little if any role. Behavioral thermoregulation is important in two ways: 1) the selection of cooler Ta values at night to prevent an excess elevation in Tc and 2) a preference for cooler Ta values before the light phase to facilitate the recovery of Tc.

Animals↗
PubMed1993

Caveats regarding the use of the laboratory rat as a model for acute toxicological studies: modulation of the toxic response via physiological and behavioral mechanisms.

The rodent, specifically the laboratory rat, is the primary experimental animal used in toxicology testing. Despite its popularity, recent studies from our laboratory and others raise a number of questions concerning the rat's appropriateness as an animal model for toxicological studies. While there may be additional areas in which the rat and other small rodents fail to adequately mimic the human response to xenobiotic agents, this article will focus on the area of temperature regulation. Thus, this article will review the thermoregulatory response of the laboratory rat following acute exposure to toxic agents and examine the impact of this response on the extrapolation of toxicological data from experimental animals to humans. In general, the rat responds to acute intoxication by lowering its core temperature via both physiological and behavioral mechanisms, thereby attenuating the induced toxicity. Similar responses have not been reported in humans.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Twenty-four hour rhythms of selected ambient temperature in rat and hamster.

The purpose of this study was to assess the effect of time of day on the behavioral thermoregulatory patterns of nocturnal rodents, the Long-Evans (LE) rat, Fischer 344 (F344) rat, and the golden hamster. Individual animals were placed in a temperature gradient for 4 days while selected ambient temperature (STa) and motor activity (MA) were monitored. Food was provided at the cold and warm ends of the gradient and water was provided ad lib. All animals eventually showed a 24-h rhythm of STa and MA characterized by a preference for cooler TaS during the dark period which coincided with an increase in MA. Both rat strains had STaS of approximately 28 degrees C during the light period that decreased to 22-24 degrees C during the dark period. The F344 rat developed a STa rhythm by the second day in the gradient, whereas the LE strain required 4 days. The hamster exhibited relatively warm STaS of 32-33 degrees C during the light period that decreased to 26-28 degrees C during the dark period. The nocturnal preference for cooler STaS contradicts a current concept of an elevation in set point of the thermoregulatory system. However, the data also suggest that behavioral and autonomic thermoregulatory effectors may operate independently in the control of night time elevations in body temperature.

Animals↗
PubMed1993

Strain comparisons of DFP neurotoxicity in rats.

The purpose of this study was to assess intraspecies differences in behavioral and autonomic function in three strains of rat following administration of diisopropyl fluorophosphate (DFP), an irreversible inhibitor of acetylcholinesterase activity. Male rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains wer administered DFP at doses of 0-1.5 mg/kg (sc). The animals were placed 60 min later into one of two motor activity chambers and tested for 30 min. Motor activity was measured using either a Doppler-based system or a commercial photocell device. Following measurement of motor activity in the Doppler system, body temperature (Tb) was measured and blood was then withdrawn by cardiac puncture and analyzed for serum cholinesterase activity (ChE). The remaining rats were retested 1 d after DFP administration in the photocell device. The results showed a significant influence of strain on the effects of DFP. Motor activity of LE rats was reduced by DFP at doses of 1.0 and 1.5 mg/kg, whereas the activity of F344 rats was reduced only at 1.5 mg/kg. The relative sensitivity of SD rats depended on the device used to measure motor activity. The SD rats resembled F344 rats in their response to DFP when motor activity was measured in the photocell device, and LE rats when motor activity was measured in the Doppler system. The Tb of F344 rats was unaffected by DFP, while the LE and SD rats became hypothermic at 1.5 mg/kg. The DFP-induced inhibition of serum ChE activity was significantly less in F344 rats. All three strains retested the day after DFP still showed significant decreases in motor activity. Overall, it appears that the F344 strain is relatively resistant to the behavioral and autonomic effects of DFP. This intraspecies variability should be considered in selecting appropriate experimental models for assessing the neurotoxicological hazards of cholinesterase-inhibiting pesticides.

Animals↗
PubMed1993

Acute and delayed effects of diisopropyl fluorophosphate on body temperature, heart rate, and motor activity in the awake, unrestrained rat.

Acute exposure to diisopropyl fluorophosphate (DFP) causes irreversible inhibition of acetylcholinesterase activity, leading to various behavioral and autonomic sequelae including hypothermia, reduced motor activity, and other neurological dysfunctions. To characterize the acute response and recovery of autonomic and behavioral processes to DFP exposure, rats of the Long-Evans strain were implanted with radiotransmitters that allowed the monitoring of core temperature, heart rate, and motor activity in unrestrained animals 24 h/d. These parameters were monitored for 96 h following subcutaneous injection of DFP at a dose of 0, 0.1, or 1.0 mg/kg. Rats given 0 and 0.1 mg/kg DFP displayed an increase in core temperature and motor activity during the first 24 h postinjection. The 1.0 mg/kg group showed a typical hypothermic response for the first 24 h following DFP administration. Core temperature decreased a maximum of 1.9 degrees C by 5 h after DFP and then started to recover, reaching control levels by 17 h after DFP treatment. Motor activity was also depressed during the first 24-h period in the 1.0 mg/kg group. Heart rate was initially elevated above basal levels in all treatment groups for several hours after treatment, but the 1.0 mg/kg group showed a decrease in heart rate at the time when core temperature began its recovery from hypothermia. Core temperature was the only parameter significantly affected by DFP during the 24-96 h recovery phase. The 0.1 and 1.0 mg/kg groups showed a significant elevation in core temperature for the 3 d after DFP administration. The elevation in core temperature during the recovery from DFP treatment may represent an important facet of the acute cholinergic neurotoxicity of organophosphate compounds.

Analysis of Variance↗
PubMed1992

Attenuation of alcohol consumption by MDMA (ecstasy) in two strains of alcohol-preferring rats.

Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. Thus, experiments were performed to determine the effect of acute and subchronic administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analog that stimulates 5-HT release, on alcohol preference in two strains of alcohol-preferring rats, the Fawn-Hooded (FH) and alcohol-preferring (P) rats. Rats were individually housed and provided free access to a solution of 10% ethanol, food, and water. Ethanol, food, and water intakes were measured daily. After establishing a stable baseline for ethanol and water intake, each rat was injected SC with a dose of 5.0 mg/kg MDMA or an equal volume of saline for 1 or 3 consecutive days. Body temperature was recorded immediately before and 120, 240, and 360 min after MDMA treatment. Ethanol, food, and water intake were measured for the preceding 24 h. Further, to determine the effect of MDMA on alcohol metabolism rats were injected with 5.0 mg/kg MDMA or saline and 15 min later with 2.5 g/kg alcohol. Then, blood alcohol levels were determined at 1, 3, and 5 h after alcohol administration. Our results show that a single administration of 5.0 mg/kg MDMA significantly decreased ethanol intake in both FH and P rats and increased water intake. Subchronic administration of 5.0 mg/kg MDMA for 3 consecutive days significantly attenuated alcohol intake in both strains but only increased water intake in P rats. Administration of MDMA induced hyper- and hypothermia in FH and P rats, respectively. This drug failed to exert any significant effect on the pharmacokinetics of alcohol, indicating a central effect.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1991

Pneumocystis carinii pneumonia in patients with solid tumors without acquired immune deficiency syndrome.

Pneumocystis carinii pneumonia (PCP) developed in two patients with solid tumors without acquired immune deficiency syndrome (AIDS). In patients with neoplastic solid tumors, as in those with hematologic malignancies, Pneumocystis is a possible cause of pneumonia. Management protocols evaluating pulmonary infiltrates in this patient population must include tests for PCP.

AIDS Serodiagnosis↗
PubMed1991

Acute effects of diisopropyl fluorophosphate (DFP) on autonomic and behavioral thermoregulatory responses in the Long-Evans rat.

Experiments were designed to assess the mechanisms of diisopropyl fluorophosphate (DFP)-induced changes in thermoregulation of the rat. In one study, male rats of the Long-Evans strain were injected with DFP (s.c.) at doses ranging from 0 to 2.0 mg/kg while maintained at an ambient temperature (Ta) of 20--24 degrees C. Body (Tb) and tail skin (Tt) temperatures were recorded for 5 h post-injection. DFP doses of greater than or equal to 1.0 mg/kg resulted in significant decreases in Tb lasting up to 5 h and increases in Tt lasting up to 1 h post-injection. In a second study, metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), Tb, and Tt were measured at 2 h post-injection of 0, 0.5, 1.0, and 1.5 mg/kg DFP (s.c.) at Ta values of 10, 20, and 30 degrees C. DFP treatment resulted in hypothermia at all three Ta values, but the effect was attenuated at 30 degrees C. MR was significantly reduced at a Ta of 20 degrees C following 1.5 mg/kg, unaffected by DFP at a Ta of 30 degrees C, and stimulated at 10 degrees C following 0.5 mg/kg DFP. EWL was significantly elevated at 30 degrees C following 1.5 mg/kg DFP. MA was significantly reduced following greater than or equal to 1.0 mg/kg DFP at 20 and 30 degrees C and 1.5 mg/kg at 10 degrees C. Tt was elevated and reduced by DFP at Ta values of 30 and 10 degrees C, respectively. In a third study, rats were injected with DFP and placed in a temperature gradient for 1 to 2 h post-injection while selected Ta and Tb were monitored. While both control and DFP-treated rats remained in the cool end of the gradient, rats administered DFP at doses of 1.0 and 1.5 mg/kg were significantly hypothermic. It was also found that Ta values of 10, 20, and 30 degrees C had no effect on DFP-induced inhibition of cholinesterase activity of plasma and erythrocyte fractions of whole blood. Overall, these data support the hypothesis that acute DFP may lower the set-point for the control of body temperature in the rat and demonstrates that the toxicity of DFP is modified by changes in Ta.

Animals↗
PubMed1991

Effects of 3,4-methylenedioxymethamphetamine on autonomic thermoregulatory responses of the rat.

3,4-Methylenedioxymethamphetamine (MDMA), a substituted amphetamine analogue which stimulates serotonin release in the CNS, has been shown to induce near lethal elevations in core temperature in the rat. To characterize the effects of MDMA on temperature regulation, we measured metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and colonic temperature (Tc) in male, Long-Evans rats at 60 min following 30 mg/kg (SC) MDMA or saline at ambient temperature (Ta) of 10, 20 and 30 degrees C. MDMA caused an elevation in MR at Ta's of 20 and 30 degrees C but had no effect at 10 degrees C. At a Ta of 30 degrees C, MR of the MDMA group was double that of the saline group. EWL was elevated by MDMA, an effect which was potentiated with increasing Ta. MDMA also elicited an increase in MA at all three Ta's. MDMA led to a 3.2 degrees C increase in Tc at 30 degrees C, no change in Tc at 20 degrees C, and a 2.0 degrees C decrease in Tc at 10 degrees C. A second study found that treatment with 20 mg/kg MDMA failed to elicit an increase in blood flow to the tail in spite of a hyperthermic core temperature of 41.4 degrees C. Preliminary studies using radiotelemetry methodology suggested that MDMA lethality is preceded by precipitous elevations in heart rate and core temperature. The data suggest that, at relatively warm Ta's. MDMA-induced stimulation of serotonergic pathways causes an elevation in MR and peripheral vasoconstriction, thus producing life-threatening elevations in Tc.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Methylenedioxyamphetamine↗
PubMed1991

Relationship between cholinesterase inhibition and thermoregulation following exposure to diisopropyl fluorophosphate in the rat.

This study examined the relationship between inhibition of cholinesterase activity (CA) and thermoregulatory response in the rat following exposure to the organophosphate (OP), diisopropyl fluorophosphate (DFP). Male Long-Evans rats were injected with DFP dissolved in peanut oil in doses ranging from 0 to 1.5 mg/kg (s.c.). Colonic (Tcol) and tail skin temperature (Ttail) were recorded at 0, 1, 2 and 3 h post-injection. At 3 h post-injection the rat was sacrificed and a blood sample was taken by cardiac puncture and analyzed for CA. There was a biphasic dose effect of DFP on Tcol with slight but significant elevation in Tcol in the dose range of 0.01-0.5 mg/kg and a significant depression in Tcol at doses of 1.0 and 1.5 mg/kg. There was a dose-dependent fall in CA with DFP administration in the erythrocyte, plasma, and whole blood fractions. Hypothermia was associated with 80-87% inhibition in CA, whereas the elevation in Tcol was associated with 20-70% inhibition in CA. DFP also elicited significant elevations in Ttail. Overall, the data fail to demonstrate any clear relationship between inhibition of blood CA and thermoregulatory response following exposure to DFP. However, the elevation in Tcol following relatively low doses of DFP may be of relevance to the frequently reported symptom of fever in humans exposed to OP agents.

Animals↗
PubMed1991

Toxic-induced hypothermia and hypometabolism: do they increase uncertainty in the extrapolation of toxicological data from experimental animals to humans?

Commonly used experimental mammals, such as the rat and mouse, exhibit hypothermia and hypometabolism when exposed acutely to many drugs and other chemical substances. This toxic-induced hypothermic/hypometabolic state may be an inherently protective response that can reduce the lethality of a toxic insult. However, as body mass increases, the ability to lower body temperature in response to toxic insult is diminished. Hence, the presence of a protective hypothermic/hypometabolic response in small laboratory mammals and apparent lack thereof in larger species, such as humans, may represent an additional physiological dissimilarity which may underestimate the risk assessment of acute toxicological data. It is proposed that acute toxicological studies in rodents be performed at relatively warm ambient temperatures (ca. 28 to 32 degrees C) to prevent toxic-induced hypothermia. This would assure a more uniform internal thermal environment between species, thus reducing a major physiological variable in species-to-species extrapolation.

Animals↗
PubMed1991

Hypothermic effects of a homologous series of short-chain alcohols in rats.

The purpose of this study was to assess the utility of the thermoregulatory system as an end point in predicting the toxicity of various short-chain alcohols. Male Fischer rats developed significant hypothermia following acute administration (ip) of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, or 2-butanol. The hypothermic responses to the six alcohols all showed similar segmented responses characterized by a threshold dose below which no change in body temperature occurred, and a suprathreshold regression with increasing dose causing greater hypothermia. Relative potency of the alcohols was assessed using both the threshold dose to cause hypothermia and the dose that would cause body temperature to decrease by 1 degree C. Both measures gave the progression of toxicity from least to most potent of methanol less than ethanol less than 2-propanol less than 1-propanol less than 2-butanol less than 1-butanol. The effective dose of each alcohol was compared to its membrane/buffer partition coefficient (Pm/b), and there was a high inverse correlation between the hypothermic dose of an alcohol and its lipid solubility. That the potency of an alcohol was strongly correlated with its Pm/b suggests that the membrane disordering theory of narcosis may also be used to explain the hypothermic action of alcohols.

Alcohols↗
PubMed1991

Comparison of rats of the Fischer 344 and Long-Evans strains in their autonomic thermoregulatory response to trimethyltin administration.

The purpose of this study was to assess the effect of genetic strain on the acute and long-term thermoregulatory response to the neurotoxicant trimethyltin (TMT) in rats of the Long-Evans (LE) and Fischer 344 (FCH) strains. In one study basic thermoregulatory responses including colonic temperature (Tc), metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), and thermal conductance (Cd) were measured in both rat strains at ambient temperatures (Ta) of 10, 28, and 37 degrees C. It was found that the LE rat has a significantly higher Tc when it is measured in their home cage. Because of its smaller body mass the FCH rat has a higher MR at all Ta values. The FCH rat also has a greater rate of EWL during exposure to a Ta of 37 degrees C. Following iv administration of 8.0 mg/kg TMT both rat strains become significantly hypothermic; however, the effect differed significantly between the strains. At 26-34 d after TMT exposure thermoregulatory responses at Ta values of 10-37 degrees C were generally similar to that of the saline controls. Overall, the LE and FCH strains of rat exhibit some distinct thermoregulatory differences in response to changes in Ta.

Animals↗
PubMed1991

Comparative effects of hypoxia on behavioral thermoregulation in rats, hamsters, and mice.

Recent studies using reptiles and other ectothermic species have shown that hypoxia lowers the set point for the control of body temperature. This is characterized by a preference for cooler ambient (Ta) and deep body temperatures (Tb) when placed in a temperature gradient. To elucidate the presence of this effect in mammals, the selected Ta and Tb of three rodent species (mouse, hamster, and rat) were measured while subjected to graded hypoxia in a temperature gradient. Individual animals were placed in the gradient for 30 min. Oxygen content of air entering the gradient was then reduced to a constant level for a period of 60 min by dilution with nitrogen. Tb was significantly reduced in all species at %O2 levels of 5.5-10%. Selected Ta was significantly reduced in the mouse at %O2 levels of 5.5 and 7.3%. Selected Ta of the hamster and rat were reduced slightly at %O2 levels of 5.8 and 7.4%, respectively; however, the effect was not statistically significant. To clarify the effects of hypoxia in these two species, the sample size of rat and hamster was increased to strengthen statistical analysis, and the animals were exposed for 60 min to %O2 levels of 7.4 and 6.7%, respectively. Both species exhibited a significant reduction in selected Ta during hypoxia concomitant with hypothermia. These data support the hypothesis that hypoxia lowers the set point for the control of body temperature in rodents.

Animals↗
PubMed1991

Dynamics of behavioral thermoregulation in the rat.

Past studies have found that the laboratory rat placed in a temperature gradient prefers temperatures that are markedly below its lower critical ambient temperature (LCT), whereas other rodents (e.g., mouse, hamster, and guinea pig) generally select thermal environments associated with minimal metabolic expenditure. To further study the rat's thermoregulatory behavior, a temperature gradient was designed to monitor the selected ambient temperature (STa) and motor activity (MA) of food-deprived rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains over a 22-h period. All three rat strains selected relatively cool STas of 21-26 degrees C during the first 1-3 h in the temperature gradient. This was followed by a gradual increase in the STa that peaked at 4 (F344) to 6 h (SD and LE) after being placed in the gradient. The LE strain had a significantly lower STa during the initial period in the gradient. There were slight decreases in the STa during the nocturnal phase in the F344 and SD strains concomitant with marked increases in MA. These results indicate that the rat requires a relatively long adjustment period in a temperature gradient before it exhibits STas that are associated with minimal metabolic expenditure. Given adequate time for accommodation, behavioral thermoregulatory responses of the rat appear to be similar to those of other rodents.

Analysis of Variance↗
PubMed1991

Proliferating trichilemmal cyst in an organoid nevus.

An unusual tumor mass of the scalp found in an elderly woman is presented. This lesion had many features simulating a verrucous squamous cell carcinoma of the scalp. Pathologic findings eventually revealed the tumor mass to be a proliferating trichilemmal cyst. Differentiation between a benign and malignant process in these lesions can sometimes be difficult. Clinical as well as histopathologic evaluation is necessary to make an accurate diagnosis.

Aged↗