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Drug modification of hypothermia induced by CNS glucopenia in the mouse
Abstract:
2-Deoxy-D-glucose (2-DG), insulin, or norepinephrine (NE), when injected into the cerebral ventricles of conscious mice, produce decreased rates of O2 consumption and hypothermia. These changes are accompanied by hyperglycemia with 2-DG, hypoglycemia with insulin, and normoglycemia with NE. Desipramine blocks the reduction in body temperature and O2 consumption produced by each of these agents, but does not modify significantly their effects on plasma glucose. The latter suggests that the thermal and oxidative responses to central glucopenia can be dissociated from concurrent alterations in circulating glucose. Propranolol enhances the hypothermic response produced by administered 2-DG, insulin, or NE. Phentolamine, however, antagonizes the hypothermia only with NE, indicating the 2-DG and insulin are probably not acting through the release of endogenous NE.
Insights
Central administration of 2-deoxy-D-glucose (2-DG), insulin, or norepinephrine (NE) decreases oxygen consumption and body temperature in mice. Desipramine blocks these effects, suggesting dissociation between central thermoregulation and glucose levels.
Area of Science:
- Neuroscience
- Physiology
- Endocrinology
Background:
- Central administration of 2-deoxy-D-glucose (2-DG), insulin, or norepinephrine (NE) can influence physiological responses.
- Investigating the central mechanisms of thermoregulation and energy metabolism is crucial for understanding physiological regulation.
Purpose of the Study:
- To investigate the effects of central 2-DG, insulin, and NE on oxygen consumption and body temperature in mice.
- To determine the role of norepinephrine and other neurotransmitters in mediating these responses.
- To explore the dissociation between central thermoregulatory effects and alterations in plasma glucose.
Main Methods:
- Injections into the cerebral ventricles of conscious mice.
- Administration of 2-DG, insulin, and NE.
- Use of pharmacological agents: desipramine and phentolamine.
- Measurement of O2 consumption, body temperature, and plasma glucose levels.
Main Results:
- Central 2-DG, insulin, and NE decreased O2 consumption and induced hypothermia.
- These effects were accompanied by hyperglycemia (2-DG), hypoglycemia (insulin), and normoglycemia (NE).
- Desipramine blocked the thermal and oxidative effects but not the glucose changes.
- Propranolol enhanced hypothermia, while phentolamine only antagonized NE-induced hypothermia.
Conclusions:
- Central glucopenia and hormonal/neurotransmitter administration trigger hypothermia and reduced O2 consumption through mechanisms dissociable from plasma glucose changes.
- Norepinephrine plays a role in mediating these central effects, but 2-DG and insulin likely act via non-adrenergic pathways.
- Desipramine's blockade suggests involvement of central pathways independent of peripheral glucose regulation.
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