Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway

Pharmacol Rep. 2021 Feb;73(1):57-72. doi: 10.1007/s43440-020-00182-3. Epub 2020 Nov 11.

Abstract

Background: The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM).

Methods: We inhibited these brain regions using cobalt chloride (CoCl2: 1.0 nmol) microinjections. We also investigated the involvement of corticotropin-releasing factor (CRF) action and protein kinase A (PKA) pathway using intra-DH and intra-VH microinjections of the CRF1 receptor antagonist CP376395 (0, 3.0, or 6.0 nmol) and the PKA inhibitor H-89 (0, 2.5, or 5.0 nmol).

Results: The results indicated that intra-VH CoCl2 microinjection increased the percentage of time spent and entries in the open arms. The mice also exhibited fewer stretch attend postures in the protected area and increased percentage of open arm entries. Further, intra-VH injection of 3.0 nmol CP376395 increased time spent in the open arms. Intra-DH injection of 6.0 nmol CP376395 increased the frequency of unprotected head dipping, whereas intra-VH injection of 6 nmol CP376395 increased the frequency of protected head dipping. Intra-VH, but not intra-DH, microinjection of 2.5 nmol H-89 increased the percentages of open arm entries and time spent in the open arms. Microinjection of 2.5 and 5.0 nmol H-89 reduced the frequency of protected head dipping behavior.

Conclusions: This study demonstrated that VH modulates anxiety-like behaviors in EPM. Moreover, CRF and the cAMP/PKA pathway seem to modulate these effects.

Keywords: Anxiety; CRF1 receptor; Corticotropin-releasing factor; Elevated plus maze; Hippocampus; Protein kinase A.

MeSH terms

  • Aminopyridines / administration & dosage
  • Aminopyridines / pharmacology
  • Animals
  • Anxiety / chemically induced*
  • Anxiety / prevention & control
  • Anxiety / psychology*
  • Behavior, Animal / drug effects
  • Cobalt / administration & dosage
  • Cobalt / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Hippocampus / drug effects*
  • Isoquinolines / administration & dosage
  • Isoquinolines / pharmacology
  • Male
  • Maze Learning / drug effects
  • Mice
  • Microinjections
  • Motor Activity
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Signal Transduction / drug effects*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology

Substances

  • (3,6-dimethyl-2-(2,4,6-trimethylphenoxy)pyridin-4-yl)(1-ethylpropyl)amine
  • Aminopyridines
  • Isoquinolines
  • Protein Kinase Inhibitors
  • Receptors, Corticotropin-Releasing Hormone
  • Sulfonamides
  • Cobalt
  • CRF receptor type 1
  • Cyclic AMP-Dependent Protein Kinases
  • cobaltous chloride
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide