Abstract
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.
(c) 2005 APA
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Behavior, Animal / drug effects
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Conditioning, Classical / drug effects
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Cyclic AMP / physiology*
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Cyclic AMP-Dependent Protein Kinases / physiology*
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Inhibitors / pharmacology
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Extinction, Psychological / drug effects
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Extinction, Psychological / physiology*
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Fear*
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Freezing Reaction, Cataleptic / drug effects
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Male
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Microinjections / methods
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Mitogen-Activated Protein Kinases / physiology*
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Narcotic Antagonists / pharmacology
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Periaqueductal Gray / drug effects
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Periaqueductal Gray / physiology*
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Rats
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Rats, Wistar
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Receptors, Opioid / physiology*
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Time Factors
Substances
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Enzyme Inhibitors
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Narcotic Antagonists
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Receptors, Opioid
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinases