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C J Gordon

Publications and source records attributed to C J Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1998

Poisons and fever.

1. Dysfunction of the thermoregulatory system is one of many pathologies documented in experimental animals and humans exposed to toxic chemicals. The mechanism of action responsible for many types of poison-induced fevers is not understood. Some elevations in body temperature are attributed to the peripheral actions of some poisons that stimulate metabolic rate and cause a forced hyperthermia. Exposure to organophosphate (OP) pesticides and certain metal fumes appears to cause a prolonged, regulated elevation in body temperature (Tb). 2. Activation of cyclo-oxygenase (COX) and the production of prostaglandin (PG)E2 in central nervous system (CNS) thermoregulatory centres is required to elicit a fever. Activating the COX-PGE2 pathway by a poison may occur by one of three mechanisms: (i) induction of cell-mediated immune responses and the subsequent release of cytokines; (ii) induction of lipid peroxidation in the CNS; and (iii) direct neurochemical activation. 3. Radiotelemetric monitoring of core temperature in unstressed rodents has led to an experimental animal model of poison-induced fever. Rats administered the OP agents chlorpyrifos and diisopropyl fluorophosphate display an initial hypothermic response lasting approximately 24 h, followed by an elevation in diurnal core temperature for 24-72 h after exposure. The hyperthermia is apparently a result of the activation of the COX-PGE2 pathway because it is blocked by the anti-pyretic sodium salicylate. Overall, the delayed hyperthermia resulting from OP exposure involves activation of thermoregulatory pathways that may be similar to infection-mediated fever.

Animals↗
PubMed1997

Behavioral thermoregulatory response to chlorpyrifos in the rat.

Chlorpyrifos (CHP) is a heavily used organophosphorous-based insecticide that elicits thermoregulatory dysfunction in the rat characterized by an initial period of hypothermia followed by a delayed hyperthermia lasting 24-72 h after exposure. The purpose of the present study was to determine (1) if the delayed hyperthermia is linked to CHP-induced hypothermia and (2) if the hypothermia and delayed hyperthermia are regulated by the CNS thermoregulatory centers. Core temperature (Tc) and motor activity (MA) of female Long-Evans rats were monitored via radiotelemetry. Rats housed in a temperature gradient were administered the control vehicle or CHP (25 mg/kg (p.o.)) while Tc, MA and ambient temperature (Ta) preferred by rats in the gradient (i.e. selected Ta) were recorded. There was an initial reduction in Tc concomitant with a decrease in selected Taa A gradual recovery in Tc occurred during the first night along with a preference for warmer Ta's and depressed MA. The day after CHP there was an elevation in Tc but no change in selected Ta, suggesting that the delayed rise in Tc was regulated. In another experiment, the hypothermic effects of CHP (25 mg/kg (p.o.)) were blocked by raising Ta from 22 to 31 degrees C immediately after CHP administration. Non-heated rats administered CHP underwent a marked period of hypothermia followed by an elevation in diurnal Tc for 2 days. Heated rats showed no hypothermic response but did undergo a hyperthermic response 48 h after CHP. MA was reduced during the first night after CHP in both non-heated and heated groups. Overall, the CHP-induced hyperthermia is not dependent on the development of hypothermia. Behavioral thermoregulatory observations suggest that both hypothermia and hyperthermia are regulated by CNS thermoregulatory centers.

Animals↗
PubMed1997

Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding.

CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic strains of HIV-1. To understand the molecular basis of the binding of chemokines and HIV-1 to CCR5, we developed a number of mAbs that inhibit the various interactions of CCR5, and mapped the binding sites of these mAbs using a panel of CCR5/CCR2b chimeras. One mAb termed 2D7 completely blocked the binding and chemotaxis of the three natural chemokine ligands of CCR5, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta, to CCR5 transfectants. This mAb was a genuine antagonist of CCR5, since it failed to stimulate an increase in intracellular calcium concentration in the CCR5 transfectants, but blocked calcium responses elicited by RANTES, MIP-1alpha, or MIP-1beta. This mAb inhibited most of the RANTES and MIP-1alpha chemotactic responses of activated T cells, but not of monocytes, suggesting differential usage of chemokine receptors by these two cell types. The 2D7 binding site mapped to the second extracellular loop of CCR5, whereas a group of mAbs that failed to block chemokine binding all mapped to the NH2-terminal region of CCR5. Efficient inhibition of an M-tropic HIV-1-derived envelope glycoprotein gp120 binding to CCR5 could be achieved with mAbs recognizing either the second extracellular loop or the NH2-terminal region, although the former showed superior inhibition. Additionally, 2D7 efficiently blocked the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. These results suggest a complicated pattern of HIV-1 gp120 binding to different regions of CCR5, but a relatively simple pattern for chemokine binding. We conclude that the second extracellular loop of CCR5 is an ideal target site for the development of inhibitors of either chemokine or HIV-1 binding to CCR5.

Animals↗
PubMed1997

Tolerance to the hypothermic and hyperthermic effects of chlorpyrifos.

Hypothermia is a commonly reported thermoregulatory response in rodents acutely exposed to organophosphates (OP); however, our laboratory has recently found a delayed hyperthermic response following the initial hypothermia when exposed to the OP, chlorpyrifos. It is well known that rodents display tolerance to OP-induced hypothermia but little is known about tolerance to OP-induced hyperthermia. Twenty female rats of the Long-Evans strain were made tolerant to chlorpyrifos by administering 0 or 10 mg/g chlorpyrifos by gavage daily for four days. Core temperature (T[c]) and motor activity (MA) were monitored continuously by telemetry. Twenty-four hours after the fourth 10 mg/kg injection, the animals were administered a challenge dose of 25 mg/kg chlorpyrifos or corn oil while the telemetry data were monitored for the next 72 h. Non-tolerant rats displayed an initial hypothermic response with reduced MA followed by a delayed increase in T(c) 24 h after exposure. The tolerant animals displayed a blunted hypothermic response with virtually no change in MA, but a delayed increase in T(c) similar to that of non-tolerant animals. The hyperthermic response of the non-tolerant animals persisted for two days, whereas the tolerant animals recovered by the second day. The data indicate that tolerance to the hypothermic and hyperthermic effects of chlorpyrifos involve separate neurochemical pathways.

Administration, Oral↗
PubMed1997

Hypothermia and delayed fever in the male and female rat exposed to chlorpyrifos.

Chlorpyrifos (CHL) is a commonly used organophosphate (OP) pesticide which irreversibly inhibits acetylcholinesterase activity in the CNS. Little is known regarding the thermoregulatory effects of CHL when administered orally and whether the sensitivity to CHL is affected by sex. To address these issues, male and female rats of the Long-Evans strain were administered 0, 10, 50, or 80 mg/kg CHL by gavage while core temperature (T(c)) and motor activity (MA) were monitored continuously by telemetry. Females were generally more sensitive than males to CHL. Significant hypothermic responses to CHL were observed in males administered 80 mg/kg and in females administered 10-80 mg/kg. Following recovery from hypothermia T(c) of both males and females underwent a significant elevation during the light phase 1-2 days after CHL exposure. CHL-induced hyperthermia was blocked in male and female rats by administration of 200 mg/kg sodium salicylate (SS), an antipyretic agent. Male castrated rats were markedly more sensitive to the hypothermic and hyperthermic effects of CHL compared to sham operated controls. On the other hand, ovariectomized female rats responded to CHL in a similar fashion as the sham operated controls. Thus, testicular function may be important in determining greater resistance to CHL in male rats. It appears that exposure to CHL leads to a delayed fever which involves activation of CNS pathways normally involved in fever. This mechanism could be responsible for the febrile response to OP pesticides commonly observed in humans exposed to OPs.

Administration, Oral↗
PubMed1997

Tracking changes in HIV-1 envelope quasispecies using DNA heteroduplex analysis.

A DNA heteroduplex tracking assay (HTA) using single-stranded probes is described. This assay provides a rapid means of resolving genetic variants coamplified by PCR and of measuring the level of particular variants in complex populations. To confidently detect minor quasispecies changes, the importance of maximizing template input into nested PCR (nPCR) and of duplicating nPCR and HTA to ensure correct population sampling is highlighted. The sensitivity of detection of rare variants within a genetically mixed population using single-stranded DNA probes is shown to be 1:500. The effects of nucleotide substitution at different locations on heteroduplex electrophoretic mobility are used to illustrate the limits of HTA for mutation detection. This simple assay may be used to track the evolution of HIV as well as to address issues of contamination and transmission.

DNA, Single-Stranded↗
PubMed1997

Behavioral and autonomic thermoregulation in the rat following propylthiouracil-induced hypothyroidism.

A reduced body temperature is a common symptom of hypothyroidism and may result from a deficiency in metabolic heat production. However, a reduced metabolism does not necessarily imply a failure in thermoregulatory control if other thermoeffectors, in particular behavioral thermoregulation, are operative. To address this issue, selected ambient temperature (Ta) in a temperature gradient, core temperature (Tc), heart rate (HR), and motor activity (MA) were monitored via radiotelemetry in euthyroid rats and rats made hypothyroid by the administration of 0.05 mg/ml propylthiouracil (PTU) in drinking water for approximately 15 days. Core temperature of PTU-treated rats was reduced by 0.3 degree, whereas selected Ta was increased by 2.3 degrees. PTU treatment led to significant reductions in HR, whereas MA was unaffected. Thermoregulatory behavior did not reverse the PTU-induced hypothermia, suggesting that PTU-induced hypothyroidism leads to a regulated reduction in body temperature (i.e., decrease in the set point). A reduced set point seems to be an adaptive response that lowers the metabolic requirements for thermoregulation in the hypothyroid rat.

Animals↗
PubMed1997

Regulated hypothermia in the hypothyroid rat induced by administration of propylthiouracil.

Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. However, it is not understood why PTU-treated animals cannot use behavioral and other thermoeffectors to maintain normal Tc. Male rats were administered PTU in drinking water (0.05 mg/ml) while the following parameters were measured: 1) Tc and motor activity (MA) recorded by radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2) selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a consistent hypothermic Tc during the light phase; however, a deficit in the stability of Tc at night was noted during exposure to 10 degrees C. In the temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C. Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of the PTU rats was maintained below 38 degrees C. The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia.

Animals↗
PubMed1996

Autonomic and behavioral thermoregulation in golden hamsters exposed perinatally to dioxin.

Perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause s a permanent change in thermoregulatory control of male offspring of the rat, characterized by a reduced core temperature (Tc over a wide range of ambient temperatures (Ta). To examine the similarities in this effect across species, the thermoregulatory effects of perinatal TCDD were evaluated in the golden hamster, a species which is very resistant to the lethal effects of TCDD. Adult male hamsters exposed on Gestational Day 11.5-11.75 to 2.0 microgram TCDD/kg by gavage were subjected to a variety of behavioral and autonomic thermoregulatory measurements. Nocturnal Tc of TCDD-treated animals was 0.4 to 1.0 degrees C below that of controls over a Ta range of 14 to 34 degrees C. Hypothermia persisted in spite of normal metabolic responses to cold exposure. The hypothermic effect of perinatal TCDD exposure was found to persist over a 24-hr period in unrestrained hamsters monitored by radiotelemetry. The TCDD-treated hamster offspring placed in a temperature gradient exhibited a preference for warm Ta's for 2 to 3 hr; however, when maintained over a 22-hr period in the gradient there was no effect of TCDD on behavioral thermoregulation. TCDD had no effect on motor activity measured over a 24-hr period. TCDD resulted in an approximately 30% reduction in body weight compared to controls; however, this weight loss appeared to have no bearing on the thermoregulatory deficiencies of the TCDD-treated animals. TCDD-treated hamsters displayed a normal metabolic response to cold exposure; thus, it would appear that perinatal exposure to TCDD leads to a dysfunction in the central control of body temperature. The perinatal effects of TCDD on thermoregulation in the rat and hamster appear to be similar.

Animals↗
PubMed1996

Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat.

Humans acutely exposed to anticholinesterase (anti-ChE) pesticides often become febrile, whereas rats and other rodents become markedly hypothermic. The rat may nonetheless be a useful model for anti-ChE toxicity because recent work using radiotelemetry demonstrated an elevation in core temperature of unrestrained rats for several days following acute exposure to the anti-ChE, diisopropyl fluorophosphate (DFP). To discern the mechanisms of DFP-induced hypothermia and hyperthermia, various pharmacological agents were administered acutely or chronically to rats injected with 1.5 mg/kg DFP (SC). Core temperature, heart rate, and motor activity were monitored continuously via radiotelemetry. Methylscopolamine, a peripheral muscarinic antagonist, attenuated the DFP-induced hypothermia by 1.0 degree C and reversed the DFP-induced bradycardia. Chronic scopolamine, a central and peripheral muscarinic antagonist, delivered via a subcutaneously implanted minipump (9.5 mg/kg/day) blocked DFP-induced hypothermia and hyperthermia. Propranolol (10 mg/kg; SC), a general beta blocker, augmented the bradycardic effects of DFP but had no effect on body temperature. Sodium salicylate (200 and 300 mg/kg; IP), an antipyretic that inhibits prostaglandin synthesis, administered during the period of DFP-induced hyperthermia produced a transient recovery in body temperature. Overall, DFP-induced hypothermia and hyperthermia in the rat appear to be mediated via cholinergic activation in the CNS because both are blocked by scopolamine. The decrease in core temperature following sodium salicylate suggests that prostaglandin release is involved in the manifestation of DFP-induced hyperthermia. The elevation in core temperature after DFP appears to involve neurochemical pathways similar to that of fever.

Adrenergic beta-Antagonists↗
PubMed1995

Assessment of offspring development and behavior following gestational exposure to inhaled methanol in the rat.

The prospect of widespread human exposure associated with its use as an alternative fuel has sparked concern about the toxic potential of inhaled methanol (MeOH). Previous studies have revealed congenital malformations in rats following inhaled MeOH (Nelson et al. (1985). Fundam. Appl. Toxicol. 5, 727-736) but these studies did not include postnatal behavioral assessment. In the present study, pregnant Long-Evans rats were placed in exposure chambers containing 15,000 ppm MeOH or air for 7 hr/day on Gestational Days (GD) 7-19. The total alveolar dose of methanol was estimated at about 6.1 g/kg/day, for a total dose of about 42.7 g/kg for the entire study. Maternal body weights were recorded daily and blood methanol concentrations were determined at the end of exposure on GD 7, 10, 14, and 18. Following birth (Postnatal Day 0 [PND 0]), a number of tests were performed at various points in development, including: offspring mortality and body wt (PND 1,3), motor activity (PND 13-21, 30, 60), olfactory learning (PND 18), behavioral thermoregulation (PND 20-21), T-maze learning (PND 23-24), acoustic startle response (PND 24, 60), reflex modification audiometry (PND 60), pubertal landmarks (PND 31-56), passive avoidance (PND 72), and visual-evoked potentials (PND 160). Maternal blood MeOH levels, measured from samples taken within 15 min after removal from the exposure chamber, declined from about 3.8 mg/ml on the first day of exposure to 3.1 mg/ml on the 12th day of exposure. MeOH transiently reduced maternal body wt (4-7%) on GD 8-10, and offspring BW (5%) on PND 1. No other test revealed significant effects of MeOH. Prenatal exposure to high levels of inhaled MeOH appears to have little effect on this broad battery of tests beyond PND 1 in the rat.

Administration, Inhalation↗
PubMed1995

Temperature regulation and metabolism in rats exposed perinatally to dioxin: permanent change in regulated body temperature?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to lower thyroxine levels and cause hypothermia in the adult rat; however, there is little known regarding the perinatal effects of TCDD on metabolism and temperature regulation of the offspring. To address this issue, thermoregulatory responses were assessed in adult male rat offspring exposed perinatally to 1.0 micrograms TCDD/kg body wt by gavage on Gestational Day 15. Individual castrated offspring were placed in a gradient-layer calorimeter for 5 hr during their nocturnal period while ambient temperature (Ta) was maintained at 10, 16, 24, or 28 degrees C. Metabolic rate (M), as measured from the total heat loss in the calorimeter, was determined along with evaporative heat loss (EHL), dry thermal conductance, and body core temperature (Tc). Animals exposed to TCDD had a significantly lower body temperature at TaS of 10, 16, and 24 degrees C and a higher thermal conductance. M was unaffected by TCDD, indicating that TCDD did not impair the effector to regulate Tc during cold exposure. EHL was also unaffected by TCDD. Skin blood flow of the interscapular area was measured in anesthetized rats with laser Doppler velocimetry and found to be the same in control and TCDD groups. The reduction in body temperature over a wide range of TaS concomitant with normal thermoregulatory effector function suggests that perinatal exposure to TCDD results in a reduction in the regulated body temperature (i.e., decrease in set-point).

Adipose Tissue, Brown↗
PubMed1995

Strain differences in the laboratory rat: impact on the autonomic, behavioral, and biochemical response to cholinesterase inhibition.

Intraspecies variation has been found to affect the physiological, behavioral, and biochemical responses to a variety of neurotoxicants, including the organophosphate diisopropyl fluorophosphate (DFP). However, there is little information on long-term physiological responses to neurotoxicant exposure using strain as a dependent variable. In the present study, radiotelemetry methodology was used to continuously monitor core temperature, heart rate, and motor activity for 4 d following administration of 1.5 mg/kg DFP (sc) in four common strains of rat: Sprague-Dawley (SD), Long-Evans (LE), Fischer 344 (F344), and Wistar (WST). The F344 rat was least susceptible to DFP in terms of both a minimal hypothermic response and recovery of the day-night difference in core temperature. The SD strain was unusual in that its heart rate was elevated relative to the other strains after DFP, in spite of a marked decrease in core temperature and motor activity. The LE strain exhibited the largest reduction in core temperature and heart rate following DFP. Serum and brain cholinesterase activity (ChE) measured 3 h after administration of 1.0 mg/kg DFP also indicated strain effects. The F344 showed less inhibition in these variables compared to the other strains, a response that may explain its attenuated thermoregulatory response to DFP. Overall, the inbred F344 rat demonstrated better resistance to DFP compared to the outbred strains. Therefore, the impact of genetic differences on sensitivity to neurotoxicants such as DFP could be an important tool in understanding the mechanism of action of these agents.

Analysis of Variance↗
PubMed1995

Trimethyltin-induced neuropathy in the rat: interaction with thermoregulation.

The enhanced production of glial fibrillary acidic protein (GFAP) by astroglia appears to be a general response of the CNS to many types of toxic insult. The organometallic neurotoxicant, trimethyltin (TMT), is one such agent known to increase the production of GFAP as a consequence of widespread neuronal destruction. TMT also leads to transient reductions in body temperature (Tb), a response which may alter the neurotoxic effects of this compound. To study the role of Tb in the neurotoxic effects of TMT, rats were injected (i.v.) with saline or 8.0 mg/kg TMT and maintained at ambient temperatures (Ta) of 16, 22, or 30 degrees C for 72 hr while Tb (core) was measured periodically. Animals were then housed at a Ta of 22 degrees C for 35 days after which time their brains were removed and dissected into hippocampus, cerebral cortex, striatum, midbrain and cerebellum for subsequent analysis of GFAP. TMT led to a significant decrease in Tb of rats housed at 22 degrees C measured 3 hr after treatment. Tb of rats maintained at Ta's of 16 and 30 degrees C was unaffected by TMT initially (i.e., no hypothermia); however, by 72 hr after TMT, rats maintained at 22 and 30 degrees C had a significantly elevated Tb. TMT led to marked elevations in GFAP levels, a response that was affected by Ta. In the hippocampus the elevation in GFAP was significantly greater in rats housed at 16 and 30 degrees C. A similar pattern was seen in the midbrain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

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

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 environmental 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 (Tsk) and core temperature (Tc) were measured at ambient temperatures (Ta) of 10, 20, 28, 30, 32, and 34 degrees C. These thermoregulatory variables were essentially unaffected by floor type at Tas of 20 and 28 degrees C. The acrylic floor showed greater increases in M, E, Tc, and Tsk, but a smaller elevation in C as Ta increased from 28 to 34 degrees C. At a Ta of 10 degrees 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 Ta of 20 degrees C. The MDMA caused Tc to increase > 2.0 degrees C in rats in the acrylic cage but had no effect on Tc 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.

3,4-Methylenedioxyamphetamine↗
PubMed1994

24-hour control of body temperature in the rat: II. Diisopropyl fluorophosphate-induced hypothermia and hyperthermia.

Diisopropyl fluorophosphate (DFP) and other anticholinesterase (antiChE) agents have been found to induce marked hypothermic responses in laboratory rodents. To characterize the effects of DFP on autonomic and behavioral thermoregulation, rats of the Long-Evans strain were injected with DFP while housed in a temperature gradient. The gradient allowed for the measurement of selected ambient temperature (Ta) and motor activity (MA) over a 6- to 7-day period. Core temperature (Tc) and heart rate (HR) were also monitored simultaneously using radiotelemetry. Injection of the peanut oil vehicle led to transient elevations in Tc, HR, and MA, but no change in selected Ta. The next day animals were injected with 0.25, 1.0, or 1.5 mg/kg DFP. DFP (1.0 AND 1.5 mg/kg) led to a marked reduction in Tc. The decrease in Tc was accompanied by reductions in HR, MA, and selected Ta. During the first night after DFP, selected Ta remained elevated as Tc recovered to its preinjection level. The second 24-h period after 1.0 and 1.5 mg/kg DFP was associated with a significant elevation in the daytime Tc. In conclusion, with the option of using behavioral thermoregulatory responses, the hypothermic effects of acute DFP treatment are mediated by a selection for cooler TaS. An elevation in Tc during recovery from acute DFP corroborates the many incidents of fever in humans exposed to anti-ChE agents.

Animals↗
PubMed1994

Autonomic and behavioral responses of selectively bred hypercholinergic rats to oxotremorine and diisopropyl fluorophosphate.

The hypercholinergic Flinders Sensitive Line (FSL) rat was significantly more sensitive than the Flinders Resistant Line (FRL) rat to the biotelemetrically recorded hypothermic effects of oxotremorine, a direct-acting muscarinic agonist, and diisopropyl fluorophosphate (DFP), an anticholinesterase agent. The effects of these agents on heart rate and motor activity, also recorded biotelemetrically, indicate either small differences (DFP) or no significant effect (oxotremorine) between the lines. These findings confirm the dramatic differences in temperature responses to cholinergic compounds between FSL and FRL rats, for which they were selectively bred, but suggest that a general increase in the sensitivity of the FSL rats to all muscarinic-mediated responses may not occur.

Animals↗