The midbrain periaqueductal gray and fear extinction: opioid receptor subtype and roles of cyclic AMP, protein kinase A, and mitogen-activated protein kinase.
Four experiments studied the opioid receptor subtype and signal transduction mechanisms mediating fear extinction in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG). Microinjection of a mu- but not a delta- or kappa-opioid receptor antagonist into the vlPAG retarded extinction. Extinction was also dose-dependently retarded by vlPAG infusions of a cyclic AMP (cAMP) analog but was unaffected by infusions of a protein kinase A activator or a mitogen-activated protein kinase inhibitor across wide dose ranges. The results show that fear extinction occurs via activation of vlPAG mu-opioid receptors and involves reductions in cAMP. These mechanisms are different from the cellular mechanisms for extinction in the amygdala and from the known cellular mechanisms for opioid analgesia in the vlPAG.
McNally
Gavan P
GP
School of Psychology, University of New South Wales, Sydney, NSW, Australia. g.mcnally@unsw.edu.au
Lee
Boo-Wahl
BW
Chiem
Janet Y
JY
Choi
Eun A
EA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D008845:Microinjections / Q000379:methods; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases