Phosphodiesterase 4 Inhibition affects both the direct and indirect pathway: an electrophysiological study examining the tri-phasic response in the substantia nigra pars reticulata

P R A Heckman, Judith Schweimer, T Sharp, T Prickaerts, A Blockland

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Fronto-striatal circuits constitute the neurobiological basis of many neuropsychiatric disorders. Part of the intracellular signaling within these circuits, including its dopaminergic modulation, is regulated by the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling cascade. Based on the overall expression in human fronto-striatal circuitry, we tested the effects of a cAMP selective phosphodiesterase 4 (PDE4) inhibitor on the tri-phasic response in the dorsomedial substantia nigra pars reticulata (SNr) upon stimulation of the infralimbic cortex in rats. Our results show for the first time that stimulation of the cognitive infralimbic cortex leads to a tri-phasic response in SNr neurons. In addition and in line with previous biochemical and behavioral studies, PDE4 inhibition by roflumilast affects the direct pathway as well as the indirect pathway of which the latter appears more sensitive than the former.
Original languageEnglish
Pages (from-to)739-748
JournalBrain Structure and Function
Volume223
Early online date18 Sept 2017
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Phosphodiesterase inhibitor
  • Roflumilast
  • Substantia nigra pars reticulata
  • Fronto-striatal circuits

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