Sex differences in the anticompulsive-like effect of memantine: involvement of nitric oxide pathway but not AMPA receptors

Behav Brain Res. 2023 Dec 22:114834. doi: 10.1016/j.bbr.2023.114834. Online ahead of print.ABSTRACTMemantine, an N-Methyl-D-Aspartate (NMDA) antagonist, has been examined as a potential treatment for Obsessive-Compulsive Disorder (OCD). Yet, there is limited knowledge regarding how it works to reduce compulsive behaviour and whether it has different effects on individuals based on their sex. Herein, we investigated if there are sex differences in the anticompulsive-like effect of memantine in adult Swiss mice. Additionally, we explored whether the nitric oxide (NO) pathway and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors play a role in memantine's effects. To start, we assessed the impact of a single intraperitoneal dose of memantine (at 3, 5, and 10mg/kg) on behaviours exhibited in the open field test (OFT) and the marble-burying test (MBT), the latter being a predictive test for anticompulsive effects. All doses of memantine reduced marble-burying behaviour in both male and female mice without affecting their locomotor activity in the OFT. This anticompulsive-like effect was also confirmed in another predictive test, the nest-building test, with the highest memantine dose (10mg/kg) reducing nest-building behaviour without significant differences between male and female mice. We observed that pre-treatment with L-arginine, a NO precursor, mitigated the anticompulsive-like effect of memantine in male mice but had no effect in female mice in the MBT. F...
Source: Behavioural Brain Research - Category: Neurology Authors: Source Type: research