title: Opioid receptors mediate direct predictive fear learning: evidence from one-trial blocking.
abstract: Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including mu-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective mu-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.
authors.affiliation: School of Psychology, The University of New South Wales, Sydney 2052, Australia.
authors.forename: Sindy
authors.initials: S
authors.lastname: Cole
authors.forename: Gavan P
authors.initials: GP
authors.lastname: McNally
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004597:Electroshock; D005239:Fear; D006614:Hindlimb; D007267:Injections; D007279:Injections, Subcutaneous; D008297:Male; D008636:Mesencephalon; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D010487:Periaqueductal Gray; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013004:Somatostatin
chemical_list: C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D010455:Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D013004:Somatostatin