Blocking of corticotrophin releasing factor receptor-1 during footshock attenuates context fear but not the upregulation of prepro-orexin mRNA in rats

• Pre-shock injections of a CRF receptor-1 antagonist attenuate contextual fear.
• Prepro-orexin mRNA levels are increased in rats exposed to footshocks.
• Antalarmin did not decrease prepro-orexin mRNA levels in shocked rats.

Hypothalamic neuropeptides called orexins (hypocretins) are well known for their roles in promoting arousal. Orexins have also been shown to play a role in fear and anxiety produced by the exposure of rats to an acute episode of moderately intense footshocks. Recent evidence indicates that stress activates orexin neurons through a corticotropin releasing factor (CRF) mechanism. In this study, we examined the effect of a CRF receptor-1 (CRF-R1) antagonist antalarmin (20 mg/kg, i.p.) given before shock exposure on subsequent expression of contextual fear and the levels of prepro-orexin (ppOX) mRNA in the hypothalamus. Antalarmin decreased fear and ultrasonic vocalization expression to the shock context at 2 and 10 days after shock exposure. However, antalarmin did not prevent the increases in ppOX mRNA produced by the shock experience. This study provides evidence that blocking of CRF-R1 at the time of footshocks attenuates contextual fear. While an increase in the activity of the orexin system may contribute to fear, this activation does not appear to be sufficient for fear expression.