Ivabradine Improves Cognitive and Behavioral Responses Following Traumatic Stress
Abstract
Alpha‐2 adrenergic receptor (α2AR) agonists, such as clonidine or dexmedetomidine, can decrease the working memory acquisition of a traumatic event, and also, blocking the post‐synaptic action of the catecholamines with a β‐adrenergic receptor (β‐AR) antagonist, propranolol, can reduce the emotional response to memories of the traumatic event. α2ARs and β‐ARs divergently regulate neuronal intracellular cyclic adenosine monophosphate (cAMP) concentrations. It is suggested that other pharmacologic mechanisms that similarly lead to reductions in neuronal cAMP could also be salutary in the treatment of post‐traumatic stress (PTSD). In the central nervous system, hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) “funny” channels are important for dendritic integration, synaptic transmission, setting membrane potential, and neuronal firing rate. These funny channels (HCN1 and HCN2) are expressed in the forebrain and pre‐frontal cortex where they are co‐located and cross talk with A2ARs that mediate intracellular cAMP concentrations and drive working memory and the emotional valence associated with memories. Also, targeted disruption of HCN gene expression, or inhibition of cyclic nucleotide binding to HCN channels in the brain, has been shown to result in antidepressant‐like behavior with improved coping in animal models of stress.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.807.7
Entities
People
- Coleman Miller
- Jeffrey Student
- Ryan Woodman
- Warren Lockette
Organizations
- Drexel University
- United States Department of Defense
- University of Michigan
- University of Missouri