Chronic treatment with antidepressants affects glycine/NMDA receptor function: behavioral evidence

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• The glycine/N-methyl D-aspartate (NMDA) receptor antagonist L-701,324 exhibits anxiolytic properties in mice, similar to benzodiazepines.
• Its anxiolytic effects are mediated through NMDA receptor antagonism and can be reversed by glycine.
• Chronic antidepressant treatments are known to influence neurotransmitter systems, potentially affecting NMDA receptor function.

Purpose of the Study:

• To investigate the impact of chronic antidepressant treatments on the anxiolytic-like effects of L-701,324.
• To explore whether chronic antidepressant administration alters NMDA receptor sensitivity or function.
• To determine if glycine can still reverse the effects of L-701,324 after chronic antidepressant exposure.

Main Methods:

• Mice were treated chronically with citalopram, imipramine, or electroconvulsive shock (ECS).
• Anxiolytic-like effects of L-701,324 were assessed using the elevated plus maze test.
• The ability of glycine to reverse L-701,324's effects was examined following chronic treatments.

Main Results:

• Chronic citalopram, imipramine, and ECS treatments significantly reduced the anxiolytic-like effects of L-701,324.
• Glycine was unable to reverse these diminished effects after chronic antidepressant exposure.
• Acute imipramine, chronic placebo, chlorpromazine, or sham ECS did not affect L-701,324's anxiolytic actions or glycine's reversal.
• Chronic imipramine did not alter the anxiolytic effect of chlordiazepoxide.

Conclusions:

• Chronic administration of various antidepressants and ECS appears to attenuate the anxiolytic-like effects of the glycine/NMDA receptor antagonist L-701,324.
• These findings support the hypothesis that chronic antidepressant treatment can modulate NMDA receptor function.
• The observed changes in NMDA receptor function may contribute to the therapeutic mechanisms of antidepressants.