Chronic Fluoxetine Treatment Desensitizes Serotoninergic Inhibition of GABAergic Inputs and Intrinsic Excitability of Dorsal Raphe Serotonin Neurons DOI Creative Commons
Wei Zhang,

Ying Jin,

Fu‐Ming Zhou

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 384 - 384

Published: April 8, 2025

Background: Dorsal raphe serotonin (5-hydroxytryptamine, 5-HT) neurons are spontaneously active and release 5-HT that is critical for normal brain function regulates mood emotion. Serotonin reuptake inhibitors (SSRIs) increase the synaptic extracellular level effective in treating depression. Treatment of two weeks or longer often required SSRIs to produce clinical benefits. The cellular mechanism underlying this delay not fully understood. Methods Results: Using whole-cell patch clamp recording slices, here we show GABAergic inputs inhibit spike firing neurons. This regulation was reduced by 5-HT; additionally, effect prevented G-protein-activated inwardly rectifying potassium (GirK) channel inhibitor tertiapin-Q, indicating a contribution activation GirK channels presynaptic axon terminals. Equally important, after 14 days treatment with fluoxetine, widely used SSRI type antidepressant, inhibition downregulated. Furthermore, chronic fluoxetine downregulated inhibitory current Conclusions: Taken together, our results suggest treatment, blocking hence increasing level, can downregulate 5-HT1B receptors on afferent terminals synapsing onto neurons, allowing extrinsic more effectively influence neurons; simultaneously, also somatic autoreceptor-activated channel-mediated hyperpolarization decrease input resistance, rendering resistant autoinhibition leading increased neuron activity. These neuroplastic changes their afferents may contribute behavioral SSRIs.

Language: Английский

Chronic Fluoxetine Treatment Desensitizes Serotoninergic Inhibition of GABAergic Inputs and Intrinsic Excitability of Dorsal Raphe Serotonin Neurons DOI Creative Commons
Wei Zhang,

Ying Jin,

Fu‐Ming Zhou

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(4), P. 384 - 384

Published: April 8, 2025

Background: Dorsal raphe serotonin (5-hydroxytryptamine, 5-HT) neurons are spontaneously active and release 5-HT that is critical for normal brain function regulates mood emotion. Serotonin reuptake inhibitors (SSRIs) increase the synaptic extracellular level effective in treating depression. Treatment of two weeks or longer often required SSRIs to produce clinical benefits. The cellular mechanism underlying this delay not fully understood. Methods Results: Using whole-cell patch clamp recording slices, here we show GABAergic inputs inhibit spike firing neurons. This regulation was reduced by 5-HT; additionally, effect prevented G-protein-activated inwardly rectifying potassium (GirK) channel inhibitor tertiapin-Q, indicating a contribution activation GirK channels presynaptic axon terminals. Equally important, after 14 days treatment with fluoxetine, widely used SSRI type antidepressant, inhibition downregulated. Furthermore, chronic fluoxetine downregulated inhibitory current Conclusions: Taken together, our results suggest treatment, blocking hence increasing level, can downregulate 5-HT1B receptors on afferent terminals synapsing onto neurons, allowing extrinsic more effectively influence neurons; simultaneously, also somatic autoreceptor-activated channel-mediated hyperpolarization decrease input resistance, rendering resistant autoinhibition leading increased neuron activity. These neuroplastic changes their afferents may contribute behavioral SSRIs.

Language: Английский

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