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Imipramine and phenelzine decrease glutamate overflow in the prefrontal cortex--a possible mechanism of
A T Michael-Titus1, S Bains, J Jeetle
1Neuroscience Research Section, Division of Biomedical Sciences, St Bartholomew's, and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Mile End Road, E1 4NS, London, UK. a.t.michael-titus@qmw.ac.uk
Neuroscience
|October 19, 2000
Summary
Antidepressants reduce glutamate release in the prefrontal cortex, potentially explaining their delayed effects on N-methyl-D-aspartate receptors and offering neuroprotection in depression.
Area of Science:
- Neuroscience
- Pharmacology
- Neurobiology
Background:
- Antidepressant efficacy mechanisms are not fully understood.
- Antidepressants affect monoamines but also other neurotransmitter systems.
- Antidepressant treatment alters N-methyl-D-aspartate (NMDA) receptor binding in the cortex.
Purpose of the Study:
- Investigate the impact of antidepressants on glutamate and aspartate release.
- Explore the link between antidepressant-induced changes in amino acid outflow and NMDA receptor alterations.
- Examine antidepressant effects in the prefrontal cortex, a region implicated in depression.
Main Methods:
- Administered imipramine and phenelzine (antidepressants) to rats.
- Measured glutamate and aspartate outflow in the prefrontal cortex and striatum.
- Assessed the onset, duration, and regional specificity of antidepressant effects on amino acid release.
Main Results:
- Antidepressants significantly decreased stimulated glutamate outflow.
- This effect was rapid, sustained with chronic administration, and specific to the prefrontal cortex.
- Findings suggest a link between reduced glutamate release and subsequent NMDA receptor changes.
Conclusions:
- Antidepressants may dampen hyperglutamatergic activity in the prefrontal cortex.
- This dampening effect could initiate NMDA receptor alterations.
- Chronic antidepressant use may possess neuroprotective potential in major depression via modulating glutamatergic activity.