Evidence map›Paper›PMID 33726625›Full record

ArticleStress (Amsterdam, Netherlands)2021

Prefrontal cortex PACAP signaling: organization and role in stress regulation.

Susan E Martelle, Evelin M Cotella, Nawshaba Nawreen, Carrie Chen, Benjamin A Packard, Maureen Fitzgerald, James P Herman

Open access · greenAbstract read
In one paragraph

Article in Stress (Amsterdam, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  3. Review
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  6. Review
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  8. PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  9. Review
  10. Article
  11. Review
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  14. Review
  15. Circulating PACAP levels are associated with increased amygdala-default mode network resting-state connectivity in posttraumatic stress disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  16. Article
  17. Review
  18. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Susan E MartelleDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Evelin M CotellaDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Nawshaba NawreenDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Carrie ChenDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Benjamin A PackardDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
Maureen FitzgeraldDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.
James P HermanDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0003-3571-2406
University of Cincinnati · USWake Forest University · US

Funding

PREDOCTORAL TRAINING PROGRAM IN THE NEUROSCIENCEST32NS007453 · NINDS · UNIVERSITY OF CINCINNATI · PI HERMAN, JAMES P · 1997 to 2025
$4.0M
Training Program in Neuroendocrinology of HomeostasisT32DK059803 · NIDDK · UNIVERSITY OF CINCINNATI · PI WOODS, STEPHEN C · 2001 to 2017
$2.8M
Assessing the role of Parvalbumin Interneurons in Adolescent Stress Induced ResilienceF31MH123041 · NIMH · UNIVERSITY OF CINCINNATI · PI NAWREEN, NAWSHABA · 2020 to 2022
$103k
Neuropeptide Mechanisms and Stress PathologiesI01BX003858 · VA · CINCINNATI VA MEDICAL CENTER RESEARCH · PI HERMAN, JAMES P · 2017 to 2020
–
BLRD VA I01 BX003858NIDDK NIH HHS T32 DK059803NIMH NIH HHS F31 MH123041NINDS NIH HHS T32 NS007453
6 · The paper itself

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuromodulatory peptide strongly implicated in nervous stress processing. Human polymorphism of the primary PACAP receptor (PAC1) is linked to psychiatric disorders, including posttraumatic stress disorder (PTSD). Prefrontal cortex PACAP signaling is associated with processing of traumatic stress and fear learning, suggesting a potential role in PTSD-related deficits. We used RNAscope to define the cellular location of PACAP and PAC1 in the infralimbic cortex (IL). Subsequent experiments used a pharmacological approach to assess the impact of IL PACAP infusion on behavioral and physiological stress response and fear memory. Adult male Sprague-Dawley rats were bilaterally microinjected with PACAP (1 ug) or vehicle into the IL, 30 minutes prior to forced swim test (FST). Blood was sampled at 15, 30, 60, and 120 minutes for analysis of hypothalamic pituitary adrenal (HPA) axis reactivity. Five days after, animals were tested in a 3-day passive avoidance paradigm with subsequent testing of fear retention two weeks later. We observed that PACAP is highly expressed in putative pyramidal neurons (identified by VGlut1 expression), while PAC1 is enriched in interneurons (identified by GAD). Pretreatment with PACAP increased active coping style in the FST, despite higher levels of ACTH and corticosterone. The treatment was also sufficient to cause an increase in anxiety-like behavior in a dark/light crossover test and enhanced retention of passive avoidance. Our data suggest that IL PACAP plays a role in driving stress responses and in processing of fear memories, likely mediated by inhibition of cortical drive.

Indexed as

Pituitary Adenylate Cyclase-Activating PolypeptideStress, PsychologicalAnimalsMalePrefrontal CortexRatsRats, Sprague-DawleyPituitary Adenylate Cyclase-Activating PolypeptidecopingForced Swim TestHPA axisPAC1passive avoidance

Identifiers

PMID33726625
PMCPMC8025233
OpenAlexW3136530701

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.