Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus
| Autor: | Hope K. Lima, Hannah M. Cavender, Lawrence M. Grover, Jennifer D. Cooke |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
Imipramine Serotonin Serotonin reuptake inhibitor Long-Term Potentiation Venlafaxine Hydrochloride Pharmacology Hippocampus Synaptic Transmission Article Reuptake Norepinephrine Norepinephrine reuptake inhibitor Fluoxetine Animals Serotonin Uptake Inhibitors Adrenergic Uptake Inhibitors biology Chemistry Brain-Derived Neurotrophic Factor musculoskeletal neural and ocular physiology Cyclohexanols Antidepressive Agents Maprotiline nervous system Norepinephrine transporter biology.protein Antidepressant Reuptake inhibitor Neuroscience Selective Serotonin Reuptake Inhibitors |
| Zdroj: | Psychopharmacology. 231:4429-4441 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-014-3587-1 |
| Popis: | Monoamine reuptake inhibitors can stimulate expression of brain-derived neurotrophic factor (BDNF) and alter long-term potentiation (LTP), a widely used model for the synaptic mechanisms that underlie memory formation. BDNF expression is upregulated during LTP, and BDNF in turn positively modulates LTP. Previously, we found that treatment with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), but not citalopram, a selective serotonin reuptake inhibitor (SSRI), reduced LTP in hippocampal area CA1 without changing hippocampal BDNF protein expression. We tested the hypothesis that combined serotonin and norepinephrine reuptake inhibition is necessary for LTP impairment, and we reexamined the potential role of BDNF by testing for region-specific changes in areas CA1, CA3, and dentate gyrus. We also tested whether early events in the LTP signaling pathway were altered to impair LTP. Animals were treated for 21 days with venlafaxine, imipramine, fluoxetine, or maprotiline. In vitro hippocampal slices were used for electrophysiological measurements. Protein expression was measured by enzyme-linked immunosorbent assay (ELISA) and Western blotting. LTP was impaired only following treatment with combined serotonin and norepinephrine reuptake inhibitors (venlafaxine, imipramine) but not with selective serotonin (fluoxetine) or norepinephrine (maprotiline) reuptake inhibitors. BDNF protein expression was not altered by venlafaxine or imipramine treatment, nor were postsynaptic depolarization during LTP inducing stimulation or synaptic membrane NMDA receptor subunit expression affected. LTP is impaired by chronic treatment with antidepressant that inhibit both serotonin and norepinephrine reuptake; this impairment results from changes that are downstream of postsynaptic depolarization and calcium influx. |
| Databáze: | OpenAIRE |
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