The Effect of Memantine Administration on Anxiety Maintenance in Stressed Male Wistar Rats

Abstract

Background: Anxiety is considered as a chronic stress complication. The role of N-methyl-D-aspartate (NMDA) glutamate receptors located in basolateral amygdala (BLA) in stress-induced anxiety is hypothesized. Objectives: It is unknown how NMDA glutamate receptors located in BLA affect maintenance of chronic stress-induced anxiety. This study investigated the role of these receptors in maintaining anxiety induced by electric foot shock in male Wistar rats. Methods: Animals were subjected to stress based on the following protocol: Seven days after bilateral cannulation in BLA, they experienced seven sessions of stress (one session/day). Before each stress session, the animals received different doses of memantine (1, 2.5, and 5 mg/kg) peripherally, or (0.1, 1 and 5 μg/kg) in BLA. Six days after stress termination, the animals were tested for maintenance of anxiety using an open field paradigm. Moreover, the animals’ brains were removed for further assessment of brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Results: The stressed animals showed anxiety six days after stress termination. Moreover, chronic peripheral and central memantine injection by itself showed both anxiolytic and anxiogenic properties six days after drug administration termination in the non-stressed animals. Memantine preadministration, both peripherally and centrally, reduced the stress-induced maintenance of anxiety in the stressed animals. The BDNF assessment revealed that stress and memantine did not change hippocampal BDNF level six days after drug or stress termination. Conclusions: Inhibition of NMDA receptors in BLA can inhibit maintenance of stress-induced anxiety, which is not related to hippocampal BDNF level. In addition, chronic memantine injection induces anxiety.