Fast glucocorticoid feedback favors 'the munchies'

Area of Science:

• Neuroendocrinology
• Molecular Neuroscience
• Behavioral Neuroscience

Background:

• Glucocorticoids (GCs) are key stress hormones with diverse physiological effects.
• Rapid, non-genomic actions of GCs in the brain are increasingly recognized.
• The precise mechanisms underlying fast GC effects on neuronal circuits remain under investigation.

Purpose of the Study:

• To elucidate the rapid molecular mechanisms by which GCs inhibit corticotropin-releasing factor (CRF) neurons.
• To investigate the role of endocannabinoids and cannabinoid receptors in GC feedback.
• To explore the potential implications for GC-mediated regulation of food intake.

Main Methods:

• Electrophysiological recordings in hypothalamic explants.
• Pharmacological manipulation of glucocorticoid and cannabinoid signaling pathways.
• Analysis of synaptic transmission and neuronal excitability.

Main Results:

• Glucocorticoids rapidly reduced excitatory glutamatergic input to CRF-synthesizing cells.
• This inhibition was mediated by endocannabinoid release acting on presynaptic CB-1 receptors.
• These findings suggest a novel, rapid feedback loop for GC regulation of CRF.

Conclusions:

• GCs rapidly inhibit CRF neurons via a membrane receptor-initiated endocannabinoid pathway.
• This endocannabinoid-mediated fast feedback inhibition is likely a widespread mechanism in the brain.
• This pathway may contribute to the rapid effects of GCs on behaviors such as food intake.