Opioid receptors in the midbrain periaqueductal gray regulate prediction errors during Pavlovian fear conditioning

The authors used a within-subject blocking design to study the role of ventrolateral periaqueductal gray (vIPAG) opioid receptors in regulating prediction errors during Pavlovian fear conditioning. In Stage I, the authors trained rats to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were copresented and followed with shock. Two novel stimuli, CSC and CSD, were also copresented and followed with shock in Stage II. CSA blocked fear from accruing to CSB. Blocking was prevented by systemic pretreatment with naloxone. Blocking was also prevented in a dose-dependent and neuroanatomically specific fashion by vIPAG infusions of the mu-opioid receptor antagonist CTAP. These experiments show that vIPAG mu-opioid receptors contribute to Pavlovian fear learning by regulating predictive error.