Basic goals of this Meeting:

--- to define the limits of heat exposure that could have harmful effects on human behavior and human health;

--- to define specific situations and conditions, which could greatly increase adverse effects of heat or heat-emitting devices on human health;

--- to define organs and systems, which are most vulnerable to heat impact.

Title of our panel “Effect of Heat on Behavior”

Eugene A. Kiyatkin MD, PhD

External Temperature ImpactExternal Temperature Impact

Adverse health consequencesAdverse health consequences

Body vvvvvvvvvvvvv

Body

Thermal homeostasis

Body vvvvvvvvvvvvv

Body

Thermal homeostasis

BRAINBRAIN

Humans have sophisticated mechanisms that maintain stability of internal temperatures following robust changes in environmental temperatures.

~3-4°C (40-41°C) stable shift in internal body temperatures could have life-threatening effects and could irreversibly damage the brain.

Therefore, I want to focus on the brain

Why the Brain?

• (1). The brain is the most important organ;

• (2). Brain tissue is exceptionally sensitive to heat, with pathological changes occurring with 3-4°C increase above normal baseline. In contrast to other tissues, many alterations occurring in the brain are irreversible, resulting in slowly developing pathologies;

• (3). Although the brain represents ~2% of the human body’s mass, it accounts for ~20% of the organism’s total oxygen consumption at rest. Since all energy used for brain metabolism appears to be finally transformed into heat, intense heat production appears to be an essential feature of brain metabolic activity;

• (4). Brain temperature and brain temperature homeostasis are poorly studied issues;

• (several examples from our experimental work on direct monitoring of brain and body temperatures during different situations in rats)

Brain/body temperatures are not stable and could fluctuate undernormal physiological conditions during physical activity, after the use of several drugs and during various motivated behaviors.

Although heat is intensively produced in brain tissue, it is effectively removed from the brain via circulation. Therefore, brain temperature could increase because of its metabolic activation and inability to properly dissipate heat by circulation.

While intense cerebral circulation is the primary means to maintain stability of brain temperatures, under several specific conditions adaptive mechanisms could fail and brain temperature could exceed normal levels.

What are these conditions?

Variability of body temperatures during normal fluctuations in activity state

Fluctuations in rectal temperatures during normal sleep-activity cycles (Engelmann, 1999)

1. Brain/body temperatures following physical exercise in adverse environmental conditions

• Physical activity results in intense heat production in the body (up to 10x). When heat could be dissipated, changes in temperature are minor (A). When heat could not be dissipated from skin surfaces, heat is accumulated in the brain, and brain and body temperatures going up to high levels (B). (from Nybo et al., 2002)

2. Internal temperatures following salient environmental stimulation

• While it is generally believed that brain and body temperature are well regulated and remain very stable, animal experiments revealed that exposure to different salient stimuli result in strong changes in brain, body and skin temperatures.

• Skin temperature decrease: peripheral vasoconstriction –additional mechanism that prevent heat dissipation to the external environment.

3. Internal temperatures following motivated behaviors

•• Feeding behavior:• --- food presentation;• --- eating (consumption)• --- brain and body

hyperthermia coupled with peripheral vasoconstriction

Male and female sexual behavior:

A1-arousing stimulation I (partner is in other cage compartment; impossible to see and interact);A2-arousing stimulation (partner is seen, but interaction is impossible);Free interactions: mounts, intromissions and ejaculations ( );

range in both sexes: 38-39.5°C

partner out – activation

(also peripheral vasoconstriction)

4. Drugs of abuse, drug self-administration, state dependency

• All drugs of abuse have a common property to induce metabolic and behavioral activation

• ! Psychomotor stimulants (cocaine, METH, MDMA)

• -- increase in brain and body t°• -- motor activation• -- peripheral vasoconstriction

5. Heroin self-administration

• robust brain and body hyperthermia (39.58C)

5. Cocaine self-administration

In contrast to heroin, cocaine SA results in weaker brain and body hyperthermia, but animals maintain relatively stable, increased temperatures during repeated drug intake)

4. METH: potentiation of hyperthermia by activity state

9 mg/kg, sc in freely moving rats in two conditions Alone + quiet rest and social interaction (presence of another animal)

Club drugs - Raves: intense physical and emotional activity, high temperature and humid environment, DRUG

•

4. METH and MDMA used under conditions that prevent normal heat dissipation

• METH and MDMA (ecstasy) at the same, high but not lethal dose at 29°C (normothermicconditions)

• Robust hyperthermia, high lethality (~70-80%); brain edema

• Dramatic increase in acute toxicity (x5-8)

•

freely moving rats

External Temperature ImpactExternal Temperature Impact

Adverse health consequencesAdverse health consequences

Body

Thermal homeostasis

Body

Thermal homeostasis

BRAINBRAIN

Activity state/Environmental

stimulation

Activity state/Environmental

stimulation

Drugs that increase metabolism and decrease heat

dissipation

Drugs that increase metabolism and decrease heat

dissipation

Ability to escapeAbilities to dissipate

metabolic heat

Ability to escapeAbilities to dissipate

metabolic heat

Conclusions:Consequences of external heat impact are drastically different depending upon environmental conditions and human activity state; they could be profoundly greater when human use drugs, which increase brain and body metabolism and diminish normal heat dissipation to the external environment.