Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment

Shengyuan Ding, Li Li, Fuming Zhou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The striatonigral projection is a striatal output pathway critical to motor control, cognition, and emotion regulation. Its axon terminals in the substantia nigra pars reticulata (SNr) express a high level of serotonin (5-HT) type 1B receptors (5-HT1BRs), whereas the SNr also receives an intense 5-HT innervation that expresses 5-HT transporters, providing an anatomic substrate for 5-HT and selective 5-HT reuptake inhibitor (SSRI)-based antidepressant treatment to regulate the striatonigral output. In this article we show that 5-HT, by activating presynaptic 5-HT1BRs on the striatonigral axon terminals, potently inhibited the striatonigral GABA output, as reflected in the reduction of the striatonigral inhibitory postsynaptic currents in SNr GABA neurons. Functionally, 5-HT1BR agonism reduced the striatonigral GABA output-induced pause of the spontaneous high-frequency firing in SNr GABA neurons. Equally important, chronic SSRI treatment with fluoxetine enhanced this presynaptic 5-HT1BR-mediated pause reduction in SNr GABA neurons. Taken together, these results indicate that activation of the 5-HT1BRs on the striatonigral axon terminals can limit the motor-promoting GABA output. Furthermore, in contrast to the desensitization of 5-HT1 autoreceptors, chronic SSRIbased antidepressant treatment sensitizes this presynaptic 5-HT1BRmediated effect in the SNr, a novel cellular mechanism that alters the striatonigral information transfer, potentially contributing to the behavioral effects of chronic SSRI treatment.

Original languageEnglish (US)
Pages (from-to)3397-3409
Number of pages13
JournalJournal of Neurophysiology
Volume113
Issue number9
DOIs
StatePublished - May 1 2015

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Receptor, Serotonin, 5-HT1B
Fluoxetine
Serotonin
GABAergic Neurons
Presynaptic Terminals
gamma-Aminobutyric Acid
Antidepressive Agents
Corpus Striatum
Autoreceptors
Inhibitory Postsynaptic Potentials
Critical Pathways
Cognition
Pars Reticulata
Inhibition (Psychology)
Emotions

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Robust presynaptic serotonin 5-HT1B receptor inhibition of the striatonigral output and its sensitization by chronic fluoxetine treatment. / Ding, Shengyuan; Li, Li; Zhou, Fuming.

In: Journal of Neurophysiology, Vol. 113, No. 9, 01.05.2015, p. 3397-3409.

Research output: Contribution to journalArticle

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