Abstract
BACKGROUND: The fronto-striatal circuits are the common neurobiological basis for neuropsychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of motor circuits, associative circuits, and limbic circuits. All circuits share 2 common features. First, all fronto-striatal circuits consist of hyper direct, direct, and indirect pathways. Second, all fronto-striatal circuits are modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cyclic adenosine monophosphate/protein kinase A signaling cascade with an additional role for the cyclic guanosine monophosphate/protein kinase G pathway, both of which can be regulated by phosphodiesterases. Phosphodiesterases are thus a potential target for pharmacological intervention in neuropsychiatric disorders related to dopaminergic regulation of fronto-striatal circuits.
METHODS: Clinical studies of the effects of different phosphodiesterase inhibitors on cognition, affect, and motor function in relation to the fronto-striatal circuits are reviewed.
RESULTS: Several selective phosphodiesterase inhibitors have positive effects on cognition, affect, and motor function in relation to the fronto-striatal circuits.
CONCLUSION: Increased understanding of the subcellular localization and unraveling of the signalosome concept of phosphodiesterases including its function and dysfunction in the fronto-striatal circuits will contribute to the design of new specific inhibitors and enhance the potential of phosphodiesterase inhibitors as therapeutics in fronto-striatal circuits.
Original language | English |
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Article number | pyw030 |
Number of pages | 16 |
Journal | International Journal of Neuropsychopharmacology |
Volume | 19 |
Issue number | 10 |
Early online date | 30 Apr 2016 |
DOIs | |
Publication status | Published - Oct 2016 |
Keywords
- fronto-striatal circuits
- dopamine
- phosphodiesterase
- phosphodiesterase inhibitors
- cyclic adenosine monophosphate
- LONG-TERM POTENTIATION
- PROTEIN-KINASE-A
- CYCLIC-AMP PHOSPHODIESTERASES
- SUBSTANTIA-NIGRA NEURONS
- QUINOLINIC ACID MODEL
- R6/2 MOUSE MODEL
- NEUROTROPHIC FACTOR
- GENE-EXPRESSION
- MESSENGER-RNA
- PDE10A INHIBITORS