Corticotropin-releasing factor (CRF) is widely distributed in the brain and coordinates behavioural responses to stress. Its receptor subtypes, CRF-R1 and CRF-R2, are expressed in the brain. For this study, we tested the effect of a continuous infusion of CRF-R2 antisense oligonucleotides into the lateral ventricle on anxiety-related behaviours in rats. Our results indicate that CRF-R2 antisense oligonucleotides produced an anxiogenic-like effect in elevated plus maze, black and white box and conditioned fear stress in rats. No significant effect on general locomotor activity was seen. These results indicate that inhibition of CRF-R2 induces an increase in anxiety-related behaviours suggesting an anxiogenic-like effect.