Hyperthermic effects on behavior

Figures & data

Table I.  Behavioral effects of hyperthermia in rats.

Animals	Exposure	Effect During Exposure	Behavioral tests	Results	Reference
Male Wistar rats; n = 14 rats/group	41°C environment for 30 min^a	Seizure	Neurodevelopmental screen	24 hrs after exposure: Advanced eye opening	[41]
			Open field	At 3 mos: ↓ activity in center of open field
			Elevated plus maze	At 3 mos: ↓ open arm time
			Forced swim	At 3 mos: no Δ^b
			Morris water maze and reversal	At 3 mos: no Δ^b
Wistar rats; n = 5–7 rats/group	Rectal temperature of 33, 37, or 39°C ± anoxia^c		Open field	At 5–30 days: ↑ % motor activity with 37 and 39°C, further ↑ anoxia At 45 days: ↑ linear velocity with 39°C	[45]
			Open field + deferoxamine	Normalized behavior
Male Wistar rats; N = 4–11 rats/group	Body temperature of 33, 37, or 39°C ± anoxia^d		Open field	At 4 mos: ↓ motor activity with ↑ temperature, further ↓ anoxia 39°C	[46]
			Open field + deferoxamine	Normalized behavior
			Elevated plus maze	At 4 mos: no Δ^b time spent and entries into open arms (trial 1), ↑ with anoxia
			Elevated plus maze + deferoxamine	Normalized behavior
			Sudden silence	At 4 mos: ↓ latency to move and ↑ motor activity with ↑ temperature
			Sudden silence + deferoxamine	At 4 mos: no Δ^b
			Telemetry – body temperature rhythm	At 4 mos: no Δ^b
			Telemetry – home-cage activity	At 4 mos: ↑ motor activity 33°C prior to plus maze test, no change afterwards
Male albino Wistar rats^e; n = 5–12 rats/group	38°C environment for ½, 1, 2, 3, or 4 hrs	∼20% rats died at 4 hrs	Rectal temperature^e	↑ with duration of heat exposure	[56]
			Salivation^e	↑ with duration of heat exposure
			Body weight^e	↓ at 4 hrs
			Prostration^e	↑ at 4 hrs
			Blood pressure^e	variable
			Arterial pH^e	no Δ^b
				↑ at 4 hrs
				↓ at 4 hrs
			Gastric hemorrhage^e	↑ with duration of heat exposure
			Tail flick^e	no Δ^b
			Rotorod^f	At 3 and 4 hrs: ↓ response
			Grid walking^f	At 3 and 4 hrs: ↓ walking and ↑ placement error
			Inclined plane^f	At 3 and 4 hrs: ↓ response
			Foot-printing^f	At 3 and 4 hrs: ↑ distance and ↓ stride-length
			Neurochemistry^f	Variable effects
			BBB permeability^f,g	At 4 hrs: ↑ permeability
			Regional blood flow in brain^f	At 4 hrs: ↓ flow
			Brain edema^f	At 4 hrs: ↑ edema
			Structural Δ^b,f	At 4 hrs: structural changes
			Rectal temperature at 4 hrs + naloxone^e,f	Attenuated^i
			Prostration at 4 hrs + naloxone^e,h	Attenuated^i
			Body weight at 4 hrs + naloxone^e,h	Attenuated^i
			Blood pressure^e,h	Attenuated^i
			Arterial pH^e,h	Attenuated^i
				Attenuated^i
				Attenuated^i
			Gastric hemorrhage + naloxone^e,h	Attenuated^i
			Inclined plane + naloxone^f,h	Normalized behavior
			Foot-printing + naloxone^f,h	no Δ^b
			Rotorod + naloxone^f,h	no Δ^b
			Grid walking + naloxone^f,h	Normalized walking, no Δ^b placement
			Neurochemistry + naloxone^f,h	Normalized
			BBB permeability^f,h	Attenuated^i
			Regional blood flow in brain + naloxone^f,h	Attenuated^i
			Brain edema^f,h	Attenuated^i
			Structural Δ^b,f,h	Attenuated^i

^aRats were exposed to hyperthermia at post-natal day 8. Rats were behaviorally tested at post-natal days 8 (before hyperthermia), 12, 14, and 16, and at 3 mos of age.

^bΔ = differences.

^cRats were exposed to anoxia for 25 min (terminated earlier if accelerated grasping occurred) and hyperthermia for 2 hrs at post-natal day 2. Rats were tested at 5, 10, 15, 20, 25, 30 and 45 day of age. Since animals within the same experimental groups did not differ between 5–30 days of life, these data were pooled.

^dRats were exposed to anoxia for 25 min (terminated earlier if accelerated grasping occurred) and hyperthermia for 2 hrs at post-natal day 2. Rats were tested at 4 mos of age.

^eTested during or immediately after heat stress at 9–10 weeks of age.

^fTested at least 4 days after heat stress.

^gBBB = blood-brain barrier.

^hNaloxone = 10 mg/kg (i.p.) dose.

ⁱAttenuated effects of hyperthermia.

Table II.  Behavioral effects of hyperthermia in humans.

Subjects	Exposure	Tests	Results	Reference
Males, ∼22 mean years of age (n = 8)	Baseline, temperate, or heat-stress conditions^a	Core body temperature	↑ heat-stress	[88]
		Random movement generation	↓ heat-stress
		Verbal short-term memory	No Δ^b
		Spatial short-term memory	No Δ^b
		Choice reaction time	No Δ^b
		Mood survey	Heat stress: ↑ fatigue, ↓ vigor
Males and females, 20–30 years of age (n = 15 subjects/group)	Four groups were run^c	Pain perception	No group differences in baseline pain scores; subsequently, pain ratings were: HS > AS + HS > AS + HS + CT > AS + CT	[102]
		Cognitive task^d	No group differences
Males and females, ∼26–32 mean years of age (n = 10)	Baseline (CON), low skin/core (LL), high skin-low core (HL), high skin/core temperature (HH) with neck-head cooling (HC)^e	Core, skin, and neck temperatures^f	Core: ↑ HH condition; no Δ^b HC Skin: ↑ HL, ↑ HH; HC ↓ HL and HH Neck: ↑ LL, ↑ HL, ↑ HH; HC ↓ LL, ↓ HL, ↓ HH	[106]
		Morse tapping task	↑ HH
		Reaction time	No Δ^b with increased skin temperature; ↓ with increased core temperature; HC had no Δ^b
		Response accuracy	No Δ^b with increased skin temperature; ↓ with increased core temperature; HC had no Δ^b
		Bond-Lader visual analogue scale	↓ alertness, contentment, calmness; HC normalized responses
		Self-perception of heat	↓ thermal comfort across all conditions; HC improved comfort in HH
Males and females, ∼31 mean years of age (n = 16)	20°C (CON), 50°C (HOT), HOT plus cold packs to head (HHC)^g	Core (thermometer pill), skin (right gastrocnemius medialis), forehead, and tympanic temperatures	All temperatures ↑ under HOT and HHC conditions;HHC ↓ core, forehead, and tympanic temperatures	[107]
		Match to sample	No Δ^b
		Choice reaction time	No Δ^b
		Rapid visual information processing	No Δ^b
		Spatial span	HOT: ↓ recall of longest sequence
		Pattern recognition memory	CON: ↓ % correct answers

^aFor baseline assessment, subjects (wearing shorts and a shirt) were behaviorally tested in an environmental chamber (36°C, 75% relative humidity, and mean radiant temperature of 35.8°C, with a wind speed of 0.6 m/sec) for 30 min 48 hrs prior to heat stress. In the temperate test, the subject (wearing shorts and a shirt) was placed into an environmental chamber (20°C with 40% relative humidity); in the heat stress condition (subject wore a polyvinyl chloride suit) the chamber was 36°C with 75% relative humidity. In both conditions, upon entering the chamber the subject began cycling for 20 min at a workload of 100 W. He rested for 10 min before repeating 20 min of cycling. After this time he rested for 70 min and took the cognitive tests. He then drank 250 ml of 40 mM NaCl solution and drank more of the solution every 20 min for a 2 hr period. After a 15 min rest, he took the behavioral tests again.

^bΔ = difference.

^cAt training each subject was exposed to thermal stimulation (46°C for 1 min) on the non-dominant thenar eminence. Subjects rated perception of pain. Subjects were randomly assigned to 4 groups: AS + CT - exposed to auditory vowel-like stimulation while performing a cognitive task, HS - exposed only to noxious heat stimulus (46°C/6 min) without the cognitive task, AS + HS - exposed to heat and auditory stimuli without the cognitive task, and AS + HS + CT - exposed to heat and auditory stimuli with the cognitive task.

^dAuditory stimulation consisted of vowel-like acoustic stimuli that had a constant frequency of 100 Hz in four formants: “the first, third, and fourth were held constant at their respective center frequencies (F1 = 500 Hz, F3 = 3500 Hz, F4 = 4300 Hz), and the second formant (F2) was modulated “in a sinusoidal fashion between 1000 and 2400 Hz.” The stimuli were presented for 2 sec at rates of 6, 8, 10, 12, or 14 Hz. The cognitive task required the subject to state whether there was a change in the rate of F2 modulation in the auditory task and whether the direction was decreasing or increasing.

^eSubjects visited the laboratory three times. In the first visit (48 hrs before test), subjects were familiarized with the tests. On the second and third visits, cognitive performance was assessed under low skin/core temperature, high skin temperature and low core temperature, and at high skin temperature and high core temperature conditions. In one experimental trial, subjects had their head and neck cooled during the cognitive tasks.

^fCore temperature was by rectal probe; skin temperatures were at midline on forehead, dorsum of the hand, lateral calf, nape of neck, and lower back.

^gAfter a familiarization session, subjects (wearing shorts and t-shirt) participated in three experimental trials with 4–7 days recovery between them. In the CON (20°C, 40% humidity, average wet-bulb globe temperature or WBGT 22.8°C), HOT (50°C, 50% humidity, WBGT 43.1°C), or HHC (WBGT 44.9°C) conditions, subjects walked on a treadmill (10–15 min) at 3–5 km/h. They rested for 45 min and then were tested for 2 hrs. The HHC condition was performed under the same environmental conditions as HOT but with three cool packs applied to the head and one to the neck that were changed every 20 min.

Table III.  Effects of radiofrequency radiation on behavior in rodents.

Animals	Exposure	Tests	Results	Reference
Male Sprague-Dawley rats (675 ± 70 g); n = 15–24 rats/group	1439 mHz pulsed time-division multiple-access field (50 Hz, 1/3 duty ratio, 6.7 msec pulse width)^a	Intraperitoneal temperature	↑ 2°C in the 25 W/kg group	[125]
		T-maze	↓ performance 25 W/kg group
Male Sprague-Dawley rats (250–300 g); n = 8 rats/group	2 μs pulses, 500 pulses/second at 2450 mHz^b	Radial arm maze	Performance of sham similar to radiated rats	[126]
Male albino Kunming mice; n = 10 mice/group	Average power densities of 5, 10, 25, or 50 mW/cm^2 for 20 min prior to each test	Rectal temperature	Temperature ↑ 0.7 and 2.3°C with 25 and 50 mW/cm^2 exposures	[127]
		Multiple-trial passive avoidance	↑ number of acquisition trials and ↓ latency to cross with 50 mW/cm^2
		Cell numbers in CA2 hippocampus	↓ with 50 mW/cm^2
		Cell numbers in amygdala	No Δ^c
Male Wistar rats (21 days of age); N = 6 rats/group morphology, n = 18 rats/group behavior	900 mHz, 0.577 msec pulse duration, 217 Hz pulse frequency for 2 hrs/day 5 days/week for 5 Weeks^d	Open field activity	No Δ^c	[128]
		Elevated plus maze	No Δ^c
		Startle response	No Δ^c
		Prepulse inhibition	No Δ^c
		Morris water maze	↑ performance in radiation-exposed rats
		Gross brain histology	No Δ^c
		Apoptosis in dentate gyrus	No Δ^c
		Doublecortin + area of granule cells	No Δ^c
		pCREB + granule cells	No Δ^c
		Blood-brain barrier permeability	No Δ^c

^aThere were two different exposure protocols. In one, rats were given acquisition training for 4 days in a T-maze, had a 4 day hiatus, and were divided into four groups: home-cage housed, sham-exposed, given a brain average SAR of 7.5 W/kg (peak SAR = 11 W/kg; whole body average SAR = 1.7 W/kg, peak SAR = 32 W/kg) for 1 hr/day, or given 25 W/kg (peak SAR = 39 W/kg; whole body average SAR = 5.7 W/kg, peak SAR = 110 W/kg) for 45 minutes. Radiation exposure was for 4 days while undergoing reversal T-maze training after each exposure. Under the second protocol, rats were run as in the first, except they were divided into three groups: home-cage housed, sham-exposed, or given a brain average SAR of 7.5 W/kg (peak 11 W/kg) for 1 hr/day for 5 consecutive days, followed by a 2-day rest-period, over three cycles.

^bThe radiation delivered a whole body SAR of 0.6 W/kg for 45 min and then were tested immediately in the maze.

^cΔ = difference.

^dAnimals were assigned to 3 different groups: sham control, a low-dose group (whole body averaged SAR of 0.3 W/kg), and a high-dose group (whole body SAR of 3 W/kg). Animals behaviorally tested or morphologically evaluated at the end of radiation exposure.

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