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MK801 impairs thermoregulation in the heat
Frédéric Canini1, Nadine Simler, Lionel Bourdon
1Département des facteurs humains, Centre de recherches du Service de santé des armées (CRSSA), La Tronche, France. fredericcanini@crssa.net
Canadian Journal of Physiology and Pharmacology
|May 7, 2002
Summary
MK801 (dizocilpine), an NMDA receptor antagonist, impairs heat regulation in rats by increasing body temperature and activity. Dopamine D1 receptor blockade did not reverse this effect, suggesting other mechanisms are involved.
Area of Science:
- Neuroscience
- Physiology
- Pharmacology
Background:
- Thermoregulation is crucial for survival, especially in extreme heat.
- Glutamate NMDA receptors and dopamine pathways play roles in regulating body temperature.
- MK801 (dizocilpine) is a known NMDA receptor antagonist with potential effects on thermoregulation.
Purpose of the Study:
- To investigate the impact of MK801 on thermoregulation in rats exposed to high ambient temperatures.
- To explore the involvement of dopamine in MK801-induced thermoregulatory deficits.
- To determine if blocking dopamine D1 receptors can mitigate MK801's effects on heat tolerance.
Main Methods:
- Adult male rats were exposed to 40°C ambient temperature.
- MK801 was administered to assess its effects on body core temperature and heat exposure duration.
- Locomotor activity and striatal dopaminergic metabolism were measured.
- Co-administration with SCH23390 (dopamine D1 receptor antagonist) was used to evaluate dopamine's role.
Main Results:
- MK801 treatment led to increased locomotor activity and a faster rise in body core temperature.
- Rats treated with MK801 reached the critical temperature of 43°C more quickly.
- Blocking dopamine D1 receptors with SCH23390 normalized locomotor activity but did not alter the heat exposure duration.
Conclusions:
- MK801 impairs thermoregulation in heat, evidenced by accelerated hyperthermia and reduced tolerance.
- The observed impairment is not primarily mediated by alterations in dopamine metabolism or increased locomotor activity.
- Further research is needed to elucidate the precise mechanisms underlying MK801's effects on heat-induced thermoregulatory failure.