We observed that blockade of KOR augmented inhibitory responses in CeA, suggesting active production of an endogenous ligand acting at KOR. Because dynorphin and norBNI also act at MOR (Munro et al., 2012; Raynor et al., 1994), we verified that the tonic activity we report was specific to KOR activation by co-applying the MOR antagonist CTAP together with norBNI. Application of norBNI alone does not affect GABAergic activity in the bed nucleus of the stria terminalis, globus pallidus or ventral tegmental area, (Ford et al., 2007; Li et al., 2012; Ogura and Kita, 2000) but serotonin release is modulated by tonic KOR activity in septal neurons (Rutz et al., 2007) and increased neuronal firing in vivo has been reported in supraoptic neurons upon administration of norBNI (Brown et al., 1998), indicative of tonic dynorphin/KOR activity regulating neuronal activity in other brain regions.
