Current Understanding of PDE10A in the Modulation of Basal Ganglia Circuitry

Adv Neurobiol. 2017;17:15-43. doi: 10.1007/978-3-319-58811-7_2.

Abstract

The basal ganglia are a forebrain network of interconnected nuclei that are involved in action selection, reward circuits and coordinating movement. PDE10A inhibition has been proposed as a novel way to modulate basal ganglia circuitry and to ameliorate symptoms in Huntington's disease, Parkinson's disease and Schizophrenia. However, despite encouraging results from pre-clinical models, PDE10A inhibitors failed to show efficacy as an antipsychotic in several clinical trials. PDE10A is expressed in the medium spiny neurons of the striatum and works to limit cyclic nucleotide signaling in response to modulatory neurotransmitters like dopamine. In this chapter, we will review the current literature on PDE10A and discuss how inhibition of PDE10A will result in alterations of the basal ganglia circuitry at the biochemical, physiological and behavioral level.

Keywords: Basal ganglia; Huntington’s Disease; PDE10A; Schizophrenia.

Publication types

  • Review

MeSH terms

  • Basal Ganglia / metabolism*
  • Dopamine / metabolism
  • Globus Pallidus / cytology
  • Globus Pallidus / metabolism
  • Humans
  • Huntington Disease / drug therapy
  • Huntington Disease / metabolism
  • Neostriatum / cytology
  • Neostriatum / metabolism*
  • Neurons / metabolism*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Phosphodiesterase Inhibitors / therapeutic use
  • Phosphoric Diester Hydrolases / metabolism*
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism
  • Signal Transduction
  • Substantia Nigra / cytology
  • Substantia Nigra / metabolism

Substances

  • Phosphodiesterase Inhibitors
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases
  • Dopamine