Treatment With Nepicastat Decreases Contextual Traumatic Memories Persistence in Post-traumatic Stress Disorder

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Martinho, R (Author) Other; Correia, G (Author) Other; Seixas, R (Author) Other; Oliveira, A (Author) Other; Silva, S (Author) Other; Maria Paula Serrão (Author) FMUP; Fernandes Lopes, C (Author) Other; Costa, C (Author) Other; Moreira Rodrigues, M (Author) ICBAS

Journal

Title: Frontiers in Molecular Neuroscience

Vol. 14

ISSN: 1662-5099

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00V-J6N

DOI: 10.3389/fnmol.2021.745219

Abstract (EN): Post-traumatic stress disorder (PTSD) is a common anxiety mental disorder and can be manifested after exposure to a real or perceived life-threatening event. Increased noradrenaline and adrenaline in plasma and urine have been documented in PTSD. Dopamine-beta-hydroxylase (DBH) catalyzes the conversion of dopamine to noradrenaline and consequently, DBH inhibition reduces catecholamines. Our aim was to evaluate if nepicastat treatment decreases PTSD signs in an animal model. Wild-type (129x1/SvJ) female mice were submitted to PTSD induction protocol. DBH-inhibitor nepicastat (30 mg/kg) or vehicle (0.2% HPMC) were administered once daily since day 0 until day 7 or 12. The percentage of freezing was calculated on days 0, 1, 2, and 7, and behavioral tests were performed. Quantification of nepicastat in plasma and DBH activity in the adrenal gland was evaluated. Catecholamines were quantified by HPLC with electrochemical detection. mRNA expression of Npas4 and Bdnf in hippocampus was evaluated by qPCR.Mice in the PTSD-group and treated with nepicastat showed a decrease in freezing, and an increase in the time spent and entries in open arms in elevated plus maze test. In mice treated with nepicastat, adrenal gland DBH activity was decreased, and catecholamines were also decreased in plasma and tissues. On day 7, in mice treated with nepicastat, there was an increase of Npas4 and Bdnf mRNA expression in the hippocampus.In conclusion, DBH inhibitor nepicastat has an effect consistent with a decrease in the persistence of traumatic memories and anxiety-like behavior in this PTSD mice model. The disruption of traumatic memories through interference with the formation, consolidation, retrieval, and/or expression processes may be important to decrease PTSD symptoms and signs. The increase in Npas4 and Bdnf mRNA expression in the hippocampus may be important to develop a weaker traumatic contextual memory after nepicastat treatment.</p>

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15