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Direct action of metyrapone on brain: implication in feeding
M R Jain1, P P Patil, N Subhedar
1Department of Pharmaceutical Sciences, Nagpur University, India.
Neuroreport
|October 25, 1993
Summary
Metyrapone, known for inhibiting corticosteroid hormones, was tested for central nervous system effects. Low doses administered centrally reduced food intake, suggesting a direct action on the brain.
Area of Science:
- Neuroendocrinology
- Pharmacology
- Behavioral Neuroscience
Background:
- Metyrapone is established to inhibit adrenal corticosteroid biosynthesis.
- The central nervous system (CNS) actions of metyrapone have not been previously investigated.
- Feeding behavior is a sensitive parameter for assessing central neurochemical effects.
Purpose of the Study:
- To investigate the potential direct central action of metyrapone.
- To determine if metyrapone influences feeding behavior via central mechanisms.
- To explore the role of the hypothalamic-pituitary-adrenal (HPA) axis in metyrapone's central effects.
Main Methods:
- Administration of low metyrapone doses (10-1000 ng) via intracerebroventricular (i.c.v.) route in a rodent model.
- Assessment of feeding behavior as a primary outcome measure.
- Functional antagonism using anti-corticotropin-releasing factor (CRF) antisera.
Main Results:
- Intracerebroventricular administration of metyrapone dose-dependently reduced food intake.
- The observed reduction in feeding behavior was antagonized by co-administration of anti-CRF antisera.
- These findings suggest a direct central effect of metyrapone on feeding regulation.
Conclusions:
- Metyrapone exerts a direct central action, influencing feeding behavior.
- The central effect of metyrapone on feeding is mediated, at least in part, by corticotropin-releasing factor (CRF).
- This study provides novel insights into the neurobiological mechanisms of metyrapone beyond its peripheral effects.