Hypothermic Mice Research Articles

Sustained hypothermia accelerates microvascular thrombus formation in mice

Cold is supposed to be associated with alterations in blood coagulation and a pronounced risk for thrombosis. We studied the effect of clinically encountered systemic hypothermia on microvascular thrombosis in vivo and in vitro. Ferric chloride-induced microvascular thrombus formation was analyzed in cremaster muscle preparations from hypothermic mice. Additionally, flow cytometry and Western blot analysis was used to evaluate the effect of hypothermia on platelet activation. To test whether preceding hypothermia predisposes for enhanced thrombosis, experiments were repeated after hypothermia and rewarming to 37 degrees C. Control animals revealed complete occlusion of arterioles and venules after 742 +/- 150 and 824 +/- 172 s, respectively. Systemic hypothermia of 34 degrees C accelerated thrombus formation in arterioles and venules (279 +/- 120 and 376 +/- 121 s; P < 0.05 vs. 37 degrees C). This was further pronounced after cooling to 31 degrees C (163 +/- 57 and 281 +/- 71 s; P < 0.05 vs. 37 degrees C). Magnitude of thrombin receptor activating peptide (TRAP)-induced platelet activation increased with decreasing temperatures, as shown by 1.8- and 3.0-fold increases in mean fluorescence after PAC-1 binding to glycoprotein (GP)IIb-IIIa and 1.6- and 2.9-fold increases of fibrinogen binding on incubation at 34 degrees C and 31 degrees C. Additionally, tyrosine-specific protein phosphorylation in platelets was increased at hypothermic temperatures. In rewarmed animals, kinetics of thrombus formation were comparable to those in normothermic controls. Concomitantly, spontaneous and TRAP-enhanced GPIIb-IIIa activation did not differ between rewarmed platelets and those maintained continuously at 37 degrees C. Moderate systemic hypothermia accelerates microvascular thrombosis, which might be mediated by increased GPIIb-IIIa activation on platelets but does not cause predisposition with increased risk for microvascular thrombus formation after rewarming.

Role of the Tumor Necrosis Factor Receptor 2 (TNFR2) in Cerebral Malaria in Mice

Infection of susceptible mice with Plasmodium berghei Anka leads to a syndrome of severe or cerebral malaria. Tumor necrosis factor (TNF) contributes to this syndrome, apparently by acting on its receptor 2 (TNFR2) because TNFR1-/- are susceptible, whereas TNFR2-/- mice are resistant. In this work, we confirmed the essential role of the TNFR2 in cerebral malaria because 6 to 8 days after Plasmodium berghei Anka infection, hypothermia, coma, and death were observed in +/+ or TNFR1-/-, but never in TNFR2-/-, mice. TNF production, evaluated by the serum levels or the mRNA levels in the brain, spleen or lung, was similar in +/+, TNFR1-/-, or TNFR2-/- mice. Macrophage or parasitized red blood cell sequestration in brain or lung was similar in TNFR1-/- and TNFR2-/- mice. Accordingly, up-regulation of CD54 or CD40 in brain or lung was also similar in TNFR1-/- or TNFR2-/- mice. Platelet loss, manifested by thrombocytopenia and the presence of microparticles in plasma, was similar in TNFR1-/- or TNFR2-/- mice. Breakdown of the blood–brain barrier, detected by the diffusion of tracers, was attenuated in both TNFR1-/- and TNFR2-/-, compared with +/+, mice. Endothelial cells from brain capillaries, examined by transmission electron microscopy, were similar in infected TNFR1-/- or TNFR2-/- mice, whereas the basement membrane was enlarged in TNFR1-/- mice. Hypothermic mice were also hyperglycemic, and this was evident in +/+ and TNFR1-/-, but not in TNFR2-/-, mice. In addition, infected +/+ and TNFR1-/- mice became insulin resistant, while in contrast TNFR2-/- became extremely insulin sensitive. This study supports the possibility that coma and death are mediated not by cell sequestration or breakdown of vascular permeability, similar in TNFR1-/- or TNFR2-/- mice, but by metabolic disturbances selectively mediated by the TNFR2.

Mechanisms of hypothermic protection against ischemic liver injury in mice.

Hepatic hypothermia can safely prolong the duration of hepatic inflow occlusion during complex liver resectional surgeries. The mechanism(s) by which hypothermia protects against this form of liver ischemia-reperfusion injury are not completely understood. In this study, we sought to determine whether hypothermia protects against ischemia-reperfusion injury by altering the hepatic inflammatory response. Mice undergoing 90 min of partial hepatic ischemia followed by up to 8 h of reperfusion had their body temperatures regulated at 35-37 degrees C (normothermic) or unregulated, in which rectal temperature dropped as low as 25 degrees C by the end of ischemia (hypothermic). Hypothermic mice had less liver injury vs. normothermic mice, as assessed histologically, by serum transaminase levels (89% decrease), and by liver wet-to-dry weight ratios (91% decrease). Neutrophil accumulation was absent in hypothermic mice (99% reduction vs. normothermic mice). Production of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and macrophage inflammatory protein-2 were reduced by up to 92%. Activation of the transcription factor nuclear factor-kappa B was not reduced in hypothermic mice, but activation of c-Jun NH(2)-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 were greatly diminished. These data suggest that hypothermia suppresses the hepatic inflammatory response through selective inhibition of JNK and AP-1.

Renal ischemia-induced increase in vascular permeability is limited by hypothermia

The purpose of the present work was to evaluate the kallikrein–kinin system and effects of hypothermia during renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min ischemia for different periods of reperfusion. Our results demonstrate that short periods of ischemia followed by reperfusion did not cause significant alterations in kallikrein activity, Evans Blue (EB) extravasation, prokallikreins, myeloperoxidase activity or plasma creatinine concentration. Edema was evident at 1 h reperfusion in the treated mice, but returned to basal values after 24 h reperfusion. Kallikrein activities and EB extravasation showed a significant increase in 60 min ischemic mice. Myeloperoxidase activity in the kidney of the mice confirmed net infiltration in the group with 60 min ischemia and 24 h reperfusion. The generation of kinins and activation of matrix degrading enzymes by tissue kallikrein, liberated from both renal and infiltrated leukocytes, could be responsible at least in part for the damage observed in the kidney of mice subject to 60 min ischemia and reperfusion. The hypothermia significantly reduced the inflammatory process in the 60 min ischemic mice, and did prevent an increase in vascular permeability. Nevertheless, the tissue edema was not shown to change between normothermic and hypothermic ischemic mice.

Do changes in body temperature following envenomation by the scorpion Leiurus quinquestriatus influence the course of toxicity?

M. Ismail, M. A. Abd-Elsalam and A. M. Morad. Do changes in body temperature following envenomation by the scorpion Leiurus quinquestriatus influence the course of toxicity? Toxicon 28, 1265–1284, 1990.—Four fatal cases following scorpion sting in children are presented. Two victims had rectal temperature above 41°C, the third exhibited a temperature of 40.9°C from the combined effects of scorpion sting and heat stroke, while the fourth was hypothermic. All victims developed hypothermia 48 hr following the sting. The hyperthermia was effectively treated by acetaminophen suppositories, ice packs and water sponges. All victims showed late hypotension that was refractory to dopamine infusion. This was explained by bradykinin released by the venom blocking the dopaminergic receptors. Deterioration of the cortical activity of the victims maintained on mechanical ventilation before the incidence of asystole suggests a central component in the cardiovascular manifestations of envenomation. A. amoreuxi venom was selected as a model for the pharmacokinetic and quantitative toxicological studies since it has no effect on body temperature. In hyperthermic rabbits injected with labelled lethal fraction of A. amoreuxi venom, there was a significant decrease in the elimination half-life, t 1 2 β , the apparent volume of the tissue compartment, V t, the apparent volume of distribution, V dss, and the intercompartmental rate constant, k CT. Hypothermic rabbits showed a significant decrease in the apparent first-order elimination rate constant, k d, and a significant increase in the elimination half-life. In both states a higher concentration of the lethal fraction in the blood was calculated. This would explain the rapidity of onset of the electrocardiographic effects and the decreased survival time in both the hyperthermic and hypothermic rabbits injected with venom when compared to normothermic animals. The s.c. ld 50 in mice and the i.v. MLD in rats were significantly reduced in the hypothermic mice and hypothermic and hyperthermic rats.

Chlorpromazine-Induced Hypothermia in Tumour-Bearing Mice, Acute Cytotoxic Drug Lethality and Long-Term Survival

The acute lethality of various cytotoxic drugs (doxorubicin, vinblastine and nitrogen mustard) and long-term survival in a syngenic mouse-tumour system were studied at normal body temperature and at 28 degrees C induced by chlorpromazine. Chlorpromazine-induced hypothermia itself neither caused acute toxicity nor influenced long-term survival. Doxorubicin (15 mg/kg) and nitrogen mustard (6 mg/kg) lethality was reduced at decreased temperature. The median survival time increased significantly from 35 days in normothermic to 52 days in hypothermic doxorubicin-treated mice. With nitrogen mustard, no increase in long-term survival was seen in the hypothermic group. The acute lethality of vinblastine was enhanced by hypothermia and the long-term tumour survival was unaffected. Hypothermia or possibly chlorpromazine considerably modulates drug toxicity and possibly anti-tumoural activity.

Nicotine antagonizes the effects of reserpine on the striatal metabolism of dopamine, 5-hydroxytryptamine and noradrenaline in hypothermic but not in normothermic mice.

Our previous studies indicate that repeated nicotine administration inhibits the release of striatal dopamine in hypothermic mice. To study if similar inhibition occurs in noradrenergic and serotoninergic neurons mice were given (-)-nicotine (3 mg/kg, s.c.) repeatedly at 110, 80, 50, and 20 min before sacrifice. The interactions of nicotine with reserpine were also investigated. Reserpine (5 mg/kg, i.p.) was administered after the second nicotine dose at 60 min before sacrifice. To prevent the effects of nicotine on autonomic ganglia all mice were given hexamethonium (10 mg/kg, i.p.). Experiments were carried out at 20-22 degrees C at which ambient temperature nicotine induced deep hypothermia or at 32-34 degrees C to prevent the drug-induced hypothermia. The changes in striatal metabolism of dopamine, noradrenaline and 5-hydroxytryptamine (5-HT) we Nicotine had temperature dependent effects on the dopamine metabolism which indicates a block of dopaminergic neurons as suggested in our earlier studies. Reserpine per se increased the homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents and decreased the 3-methoxytyramine (3-MT) and dopamine contents at both ambient temperatures. In hypothermic but not in "normothermic", nicotine-treated mice reserpine's effect on dopamine metabolism was almost totally vanished. Nicotine and reserpine per se increased the 3-methoxy-4-hydroxyphenylethylglycol (MOPEG) content and decreased the noradrenaline content at both ambient temperatures. In hypothermic but not in "normothermic" mice nicotine antagonized the reserpine-induced decrease of noradrenaline content. Nicotine tended to decrease the 5-hydroxy-indoleacetic acid (5-HIAA) content in hypothermic mice but increased it in "normothermic" ones.(ABSTRACT TRUNCATED AT 250 WORDS)

Dual Effects of Nicotine on Neuroleptic‐Induced Changes of Striatal Dopamine Metabolism in Mice

The effect of nicotine on the neuroleptic-induced changes in striatal dopamine (DA) metabolism of mice was studied. To investigate the mechanism of action of nicotine, its interactions with apomorphine (APO) and gamma-hydroxybutyric acid (GHBA) were also investigated. Mice were given nicotine, (0.3-3 mg/kg subcutaneously) repeatedly (4 times) at 30 min. intervals. Haloperidol (HAL), (+/-)-sulpiride (SUL), APO or GHBA were administered after the second nicotine dose. Hexamethonium was given to prevent the effects of nicotine on autonomic ganglia. The striatal contents of DA and of its metabolites homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were measured. The drug-induced hypothermia in mice was controlled by increasing ambient temperature. At ambient temperature of 32-34 degrees nicotine and HAL increased the striatal DOPAC and HVA contents additively, whereas APO counteracted the effects of nicotine at this ambient temperature. At 20-22 degrees nicotine decreased the 3-MT content which indicates reduced release of DA. In hypothermic mice nicotine inhibited better the HAL- and SUL-induced increases of HVA content than those of DOPAC content suggesting that the neuroleptic-induced increases in DOPAC and HVA contents are mediated partly by different mechanisms. In APO-treated mice both the GHBA- and nicotine-induced decreases of 3-MT content fell further. GHBA did not alter the nicotine-induced decrease of 3-MT content and so this effect of nicotine may be mediated indirectly via GABAergic neurones. Unlike GHBA and APO nicotine decreased 3-MT content only in hypothermic mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ethyl alcohol on thermoregulation in mice following the induction of hypothermia or hyperthermia

This study was designed to assess the effects of ethyl alcohol (ethanol) administration on behavioral and autonomic thermoregulation in mice subjected to severe hypothermia or hyperthermia. Male mice of the BALB/c strain were injected intraperitoneally with ethanol at dosages of 0, 0.3, 1.0, or 3.0 g/kg and then placed within a hot environmental chamber to raise their body temperature to 41°C or, alternatively, within a cold chamber to lower it to 28°C. Once the desired hypothermic or hyperthermic state was achieved, the mice were removed from the chamber and placed in either a temperature gradient to monitor behavioral thermoregulatory responses or in an environmental chamber thermostabilized at an ambient temperature (T a) of 28°C to monitor metabolic rate. The 3.0 g/kg dosage significantly affected behavioral thermoregulatory responses of the hyperthermic mice when initially placed in the temperature gradient. The ability to increase metabolic rate following hypothermia was significantly suppressed at 3.0 g/kg. Dosages of 1.0 and 3.0 g/kg inhibited metabolic rate of hyperthermic mice. Both hypothermic and hyperthermic mice given 3.0 g/kg of ethanol had colonic temperatures significantly below normal after placement in the temperature gradient and metabolic chamber. In conclusion, relatively large dosages of ethanol impair behavioral and autonomic thermoregulation and may lower the set-point for the control of body temperature in mice.

Different changes in striatal dopamine metabolism induced by nicotine in mice kept at different ambient temperatures. Evidence for partly separate metabolic routes of dopamine derived from separate compartmentations.

Further information about the nicotine-induced changes in striatal dopamine metabolism in hypothermic mice was searched by measuring the contents of dopamine and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; 3-methoxytyramine, 3-MT; and homovanillic acid, HVA) after blocking the synthesis of dopamine by alpha-methyl-p-tyrosine (alpha-MT). This method gave a possibility to study the effect of nicotine on the metabolism of dopamine in two pools (the cytoplasmic "newly-synthesized" dopamine and the granular dopamine). 3 mg/kg of (-)nicotine was given s.c. four times, at 110, 80, 50 and 20 min, and alpha-MT (250 mg/kg i.p.) at 60 min before sacrifice. To prevent the peripheral effects of nicotine all mice were given hexamethonium (10 mg/kg i.p.) at 140 min before sacrifice. Hexamethonium did not alter striatal dopamine metabolism. Experiments were performed at 20-22 degrees C at which temperature nicotine induced hypothermia or at 32-34 degrees C. The alpha-MT-induced proportional decrease of 3-MT content was clearly less than that of dopamine content. On the contrary the alpha-MT treatment decreased the DOPAC content proportionally more than the dopamine content. Thus DOPAC could not be solely formed from the same dopamine pool as 3-MT. These results indicate that 3-MT reflects best the metabolism of the granular dopamine and DOPAC that of the "newly-synthesized" dopamine. In hypothermic mice nicotine administration reduced the alpha-MT-induced depletion of the dopamine content.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of Microwave Heating in 5-Hydroxytryptamine-Induced Hypothermic Mice

The intraperitoneal injection of 5-hydroxytryptamine (5-HT) in unrestrained and unanesthetized mice held at 22°C causes a hypothermia which is maximal after approximately 15 min. When mice injected with 5-HT were held in a controlled environment of 22°C and 50% relative humidity and exposed to microwaves (2450 MHz, cw) at $1 {\rm mW}/{\rm cm}^{2}$ for 15 min, significant significant increases were observed in the body temperature of these mice compared to 5-HT-treated sham-irradiated mice. The magnitude of the response was related to power density ( $10>5>1 {\rm mW}/{\rm cm}^{2}$ ). Saline-injected mice exposed for 15 min at 10 mW/ cm2 (specific absorption rate = 7.2 m W/g) showed no significant increase in body temperature compared to saline-injected sham-irradiated mice. The hypothermia induced by 5-HT in mice was also found to be affected by ambient temperature alone. Increases in ambient temperature above 22°C, in the absence of microwaves, caused a concomitant incr...

Evidence of state dependent learning of brightness discrimination in hypothermic mice

Shock-elicited escape behavior of C57Bl mice in a brightness discrimination task was examined to investigate the effects of hypothermia on acquisition and reversal. Neither acquisition nor reversal was impaired by 7°C or 13°C decreases in central body temperature when body temperature remained at those levels throughout testing. However, body temperature changes from acquisition to reversal were accompanied by memory deficits during reversal if acquisition occurred at body temperature decreased by 13° and reversal occurred at normal body temperature or body temperature decreased by 7°. Memory deficit was not observed in groups given acquisition at normal body temperature or body temperature decreased by 7° and reversal at body temperature decreased by 13°. This finding suggests the occurrence of a state dependent discrimination response: an instance of asymmetrical dissociation. In addition, during acquisition, latency of the escape response was longer in hypothermic animals than in controls, and should be interpreted as a performance deficit, rather than failure or delayed rate of learning. Depressed intertrial activity also was observed in hypothermic animals.

Alteration of hepatic polyribosome structure and function in mice during hypothermia

Analysis of the distribution of RNA double labeled with [ 14C]- and [ 3H]orotic acid in ribosomal particles separated by sucrose density-gradient centrifugation and the selective dissociation of unprogrammed ribosomes showed that the increase in proportion of monomeric ribosomes caused by hypothermia is due entirely to the increase in the unprogrammed ribosome fraction at the expense of polyribosomes. Protein synthetic activities of polyribosomes in vivo in livers of hypothermic and control mice were compared by double labeling of nascent and soluble polypeptides with [ 14C]- and [ 3H]leucine. Incorporation of radioactivity was relatively higher in nascent polypeptides and lower in soluble polypeptides in hypothermic than in control mice. The results indicate that hypothermia affects protein synthesis in livers of mice by decreasing probably the rates of both initiation and elongation, but affecting the former more than the latter.

CYCLIC NUCLEOTIDES IN MURINE BRAIN: EFFECT OF HYPOTHERMIA ON ADENOSINE 3′,5’ MONOPHOSPHATE, GLYCOGEN PHOSPHORYLASE, GLYCOGEN SYNTHASE AND METABOLITES FOLLOWING MAXIMAL ELECTROSHOCK OR DECAPITATION

Abstract—The accumulation of adenosine‐3′,5′‐cyclic monophosphate (cyclic AMP) has been investigated in murine brain following electroconvulsive shock and decapitation. Animals were made hypothermic (20°C) to minimize the freezing time of the brain and to delay metabolic events. Cyclic AMP concentrations were decreased in the cerebral cortex of hypothermic rats and mice. Furthermore, the changes in cyclic AMP elicited by electroconvulsive shock and decapitation were delayed. In hypothermic animals, the metabolic rate as determined by high energy phosphate use was decreased to 65% of control values. The interconversions of the active and inactive forms of glycogen phosphorylase and glycogen synthase were sufficiently retarded in hypothermic animals to correlate with changes in cyclic AMP concentrations. The conversion of phosphorylase b to a and synthase a to b occurred when cyclic AMP concentrations had increased from 2 to 5 μmol/kg, following either electroconvulsive shock or decapitation. The results indicate that cyclic AMP plays a role in regulation of glycogen metabolism in cerebral cortex.

Blood pressure changes in mice after lethal staphylococcal infection and endotoxin challenge.

A radioisotope technique has been used to determine blood pressure changes in mice after lethal staphylococcal infection and after lethal endotoxin challenge. The method was verified by making simultaneous direct measurements in rats. Mice in both groups became hypotensive to a similar level (a fall 20-30 mm Hg). This tailcuff technique is simple and reliable but is dependent upon normal tail blood flow. Spurious low pressure readings are obtained in hypothermic or chilled mice because the tail is a major thermoregulator organ. These difficulties can be overcome by warming chilled or hypothermic mice.

Microcirculatory Changes and General Responses to 5‐Hydroxytryptamine in Normothermic and Hypothermic Mice

AbstractSvanes, K. Microcirculatory changes and general responses to 5‐Hydroxytryptamine in Normothermic and hypothermic mice. Acta physiol. scand. 1968. 72. 404–411.5‐hydroxytryptamine (5‐HT) was injected i.v. into unanesthetized, anesthetized normothermic and hypothermic (21–22° C) mice, and the general effects of the injections were observed. In addition, conjunctival microscopy and hematocrit determinations were performed. 5‐HT was found to cause a syndrome characterized by exophtalmus, respiratory distress, cyanosis, edema, evacuation of bowels, salivation, lethargy, constriction and slow blood flow in the metarterioles, dilatation and stasis in the venules, and hemoconcentration. In general the reaction to 5‐HT was relatively mild in unanesthetized mice, moderate in anesthetized normothermic mice and severe in hypothermic mice. The marked reaction to 5‐HT under hypothermia might be due to retarded elimination of 5‐HT from the blood.

Microcirculatory changes and general responses to 5-hydroxytryptamine in normothermic and hypothermic mice.

Svanes, K. Microcirculatory changes and general responses to 5-Hydroxytryptamine in Normothermic and hypothermic mice. Acta physiol. scand. 1968. 72. 404–411. 5-hydroxytryptamine (5-HT) was injected i.v. into unanesthetized, anesthetized normothermic and hypothermic (21–22° C) mice, and the general effects of the injections were observed. In addition, conjunctival microscopy and hematocrit determinations were performed. 5-HT was found to cause a syndrome characterized by exophtalmus, respiratory distress, cyanosis, edema, evacuation of bowels, salivation, lethargy, constriction and slow blood flow in the metarterioles, dilatation and stasis in the venules, and hemoconcentration. In general the reaction to 5-HT was relatively mild in unanesthetized mice, moderate in anesthetized normothermic mice and severe in hypothermic mice. The marked reaction to 5-HT under hypothermia might be due to retarded elimination of 5-HT from the blood.

The Effect of Barbiturate Anesthesia and Hypothermia on the Edema Formation Caused by Subcutaneous Injection of 5‐Hydroxytryptamine in Mice

AbstractLocal edema formation caused by subcutaneous injection of 5‐hydroxytryptamine (5‐HT) was studied in unanesthetized, anesthetized normothermic and hypothermic mice. The edema was estimated quantitatively by a method involving the assay of extravasated trypan blue. Pentobarbital was used for anesthesia. The hypothermic mice were kept at a rectal temperature of 21–22° C. In unanesthetized and anesthetized normothermic mice the edema formation increased with increasing doses of 5‐HT. At normal temperature light anesthesia greatly reduced the edema caused by 100 μg/ml 5‐HT, but did not modify the edema caused by 10 or 1 μg/ml 5‐HT. A lowering of the body temperature led to reduced edema formation, and the edema caused by 100 μg/ml 5‐HT was relatively more reduced than that caused by 10 μg/ml 5‐HT. The reduced edema formation under anesthesia and hypothermia might in part be due to increased constriction of the local arteries and arterioles under these conditions.

The effect of barbiturate anesthesia and hypothermia on the edema formation caused by subcutaneous injection of 5-hydroxytryptamine in mice.

AbstractLocal edema forniation caused by subcutaneous injection of 5‐hydroxytryptamine (5‐HT) was studied in unanesthetized, anesthetized normothermic and hypothermic mice. The edema was estimated quantitatively by a method involving the assay of extravasated trypan blue. Pento‐barbital was used for anesthesia. The hypothermic mice were kept at a rectal temperature of 21–22 C. In unanesthetized and anesthetized normothermic mice the edema formation increased with increasing doses of 5‐HT. At normal temperature light anesthesia greatly reduced the edema caused by 100 μg/ml 5‐HT, but did not modify the edema caused by 10 or 1 μg/ml 5‐HT. A lowering of the body temperature led to reduced edema formation, and the edema caused by 100 μg/ml 5‐HT was relatively more reduced than that caused by 10 μg/ml 5‐HT. The reduced edema formation under anesthesia and hypothermia might in part he due to increased constriction of the local arteries and arterioles under these conditions.

REDUCTION OF RETROACTIVE EFFECTS OF INTERPOLATED MAZE TRAINING IN HYPOTHERMIC MICE.

In two experiments the retroactive effect of maze training interpolated between an initial acquisition phase and a testing phase was determined in mice. In the first experiment a retroactive inhibitory effect was demonstrated in animals given interpolated training for the reversal of an acquired maze response. In the second experiment the interpolated activity was either habit reversal, overtraining, or practice swimming. When the interpolated activity was initiated in the presence of hypothermia habit reversal did not occur, no retroactive inhibition was shown, and facilitation of performance from overtraining or practice swimming was negated. The data support the hypothesis that hypothermia maintained during maze training reduces the negative (retroactive inhibition) as well as positive (facilitation) effects that such training has upon the performance of a previously acquired maze habit. maze learning in mice; maze acquisition during hypothermia; hypothermia and interpolated maze training; animal behavior; learning in hypothermic animals; hypothermia and maze acquisition Submitted on January 16, 1964