Abstract | RATIONALE: OBJECTIVES: First, we evaluated NOP receptor antagonism on general behavioral performance and again following a three-species predator exposure model (Experiment 1). Then, we evaluated effects of NOP antagonism on fear memory expression (Experiment 2). METHODS: Adult, male rats underwent daily administration of NOP antagonists ( J-113397 or SB-612,111; 0-20 mg/kg, i.p.) and testing in acoustic startle, elevated plus maze, tail-flick, and open field tests. Effects of acute NOP antagonism on behavioral performance following predator exposure were then assessed. Separately, rats underwent fear conditioning and were later administered SB-612,111 (0-3 mg/kg, i.p.) prior to fear memory expression tests. RESULTS:
J-113397 and SB-612,111 did not significantly alter most general behavioral performance measures alone, suggesting minimal off-target behavioral effects of NOP antagonism. J-113397 and SB-612,111 restored performance in measures of exploratory behavior (basic movements on the elevated plus maze and total distance in the open field) following predator exposure. Additionally, SB-612,111 significantly reduced freezing behavior relative to control groups across repeated fear memory expression tests, suggesting NOP antagonism may be useful in dampening fear responses. Other measures of general behavioral performance were not significantly altered following predator exposure. CONCLUSIONS: NOP antagonists may be useful as pharmacotherapeutics for dampening fear responses to trauma reminders, and the present results provide supporting evidence for the implication of the NOP system in the neuropathophysiology of dysregulations in fear learning and memory processes observed in trauma- and stress-related disorders.
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Authors | Rachel M Taylor, Isaac H Jeong, Matthew D May, Elizabeth M Bergman, Vincent F Capaldi, Nicole L T Moore, Liana M Matson, Emily G Lowery-Gionta |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 237
Issue 10
Pg. 2943-2958
(Oct 2020)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 32588078
(Publication Type: Journal Article)
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Chemical References |
- Benzimidazoles
- Cycloheptanes
- J 113397
- Opioid Peptides
- Piperidines
- Receptors, Opioid
- cis-1-methyl-7-((4-(2,6-dichlorophenyl)piperidin-1-yl)methyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol
- nociceptin
- Nociceptin Receptor
- Oprl protein, rat
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Topics |
- Animals
- Benzimidazoles
(administration & dosage)
- Cycloheptanes
(administration & dosage)
- Dose-Response Relationship, Drug
- Exploratory Behavior
(drug effects, physiology)
- Fear
(drug effects, physiology, psychology)
- Male
- Memory
(drug effects, physiology)
- Opioid Peptides
(antagonists & inhibitors, metabolism)
- Piperidines
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Receptors, Opioid
(metabolism)
- Stress Disorders, Post-Traumatic
(drug therapy, metabolism, psychology)
- Nociceptin Receptor
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