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Heckman PRA, van Duinen MA, Bollen EPP, et al. Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications. Int J Neuropsychopharmacol. 2016;19(10)doi: 10.1093/ijnp/pyw030.
Heckman, P. R. A., van Duinen, M. A., Bollen, E. P. P., Nishi, A., Wennogle, L. P., Blokland, A., & Prickaerts, J. (2016). Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications. The international journal of neuropsychopharmacology, 19(10), . https://doi.org/10.1093/ijnp/pyw030
Heckman, Pim R A, et al. "Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications." The international journal of neuropsychopharmacology vol. 19,10 (2016). doi: https://doi.org/10.1093/ijnp/pyw030
Heckman PRA, van Duinen MA, Bollen EPP, Nishi A, Wennogle LP, Blokland A, Prickaerts J. Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications. Int J Neuropsychopharmacol. 2016 Apr 02;19(10). doi: 10.1093/ijnp/pyw030. PMID: 27037577; PMCID: PMC5091819.
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Int J Neuropsychopharmacol. 2016 Apr 02;19(10). doi: 10.1093/ijnp/pyw030.

Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications.

The international journal of neuropsychopharmacology

Pim R A Heckman, Marlies A van Duinen, Eva P P Bollen, Akinori Nishi, Lawrence P Wennogle, Arjan Blokland, Jos Prickaerts

PMID: 27037577 PMCID: PMC5091819 DOI: 10.1093/ijnp/pyw030

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.

© The Author 2016. Published by Oxford University Press on behalf of CINP.

Keywords: cyclic adenosine monophosphate; dopamine; fronto-striatal circuits; phosphodiesterase; phosphodiesterase inhibitors

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