Paliperidone increases spontaneous and evoked firing of mesocortical dopaminergic neurons by activating a hyperpolarization-activated inward current

Haiman Dong, Qian Wang, Dexiao Zhu, Fei Gao, Hui Wang, Lihua Bao, Jing Zhang, Yanlai Hu, Zhaoxi Ding, Jinhao Sun

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20 μmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P < 0.05). Moreover, paliperidone also increased the frequency of evoked action potentials by current injection stimulation (P < 0.05), whereas the accompanying amplitude decreased. Furthermore, to explore the mechanisms of paliperidone's effect, Ih currents were detected, and the results showed that hyperpolarizing voltage pulses evoked instantaneous Ih inward currents and paliperidone increased the maximum Ih current. In addition, paliperidone decreased the spontaneous inhibitory postsynaptic currents. Thus, paliperidone increased the spontaneous and evoked firing of mesocortical neurons, possibly by activating the Ih inward current and reducing the inhibitory synaptic transmission, which provides an underlying mechanism of paliperidone's application in schizophrenia.

Original languageEnglish (US)
Pages (from-to)252-258
Number of pages7
JournalSchizophrenia research
Volume176
Issue number2-3
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Keywords

  • Dopaminergic
  • I current
  • Mesocortical
  • Paliperidone

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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