Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances

Abstract Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic...

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Autores principales:	Zachary Freyberg, Michael J. McCarthy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/b1ff6b62c4e34477b018d828f67cbac8
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spelling	oai:doaj.org-article:b1ff6b62c4e34477b018d828f67cbac82021-12-02T11:51:10ZDopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances10.1038/s41537-017-0018-42334-265Xhttps://doaj.org/article/b1ff6b62c4e34477b018d828f67cbac82017-04-01T00:00:00Zhttps://doi.org/10.1038/s41537-017-0018-4https://doaj.org/toc/2334-265XAbstract Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic drugs may cause these important side effects to varying degrees. Given that the single unifying property shared by these medications is blockade of dopamine D2 and D3 receptors, these receptors likely play a role in antipsychotic drug-induced metabolic side effects. Dopamine D2 and dopamine D3 receptors are expressed in brain regions critical for metabolic regulation and appetite. Surprisingly, these receptors are also expressed peripherally in insulin-secreting pancreatic beta cells. By inhibiting glucose-stimulated insulin secretion, dopamine D2 and dopamine D3 receptors are important mediators of pancreatic insulin release. Crucially, antipsychotic drugs disrupt this peripheral metabolic regulatory mechanism. At the same time, disruptions to circadian timing have been increasingly recognized as a risk factor for metabolic disturbance. Reciprocal dopamine and circadian signaling is important for the timing of appetitive/feeding behaviors and insulin release, thereby coordinating cell metabolism with caloric intake. In particular, circadian regulation of dopamine D2 receptor/dopamine D3 receptor signaling may play a critical role in metabolism. Therefore, we propose that antipsychotic drugs’ blockade of dopamine D2 receptor and dopamine D3 receptors in pancreatic beta cells, hypothalamus, and striatum disrupts the cellular timing mechanisms that regulate metabolism. Ultimately, understanding the relationships between the dopamine system and circadian clocks may yield critical new biological insights into mechanisms of antipsychotic drug action, which can then be applied into clinical practice.Zachary FreybergMichael J. McCarthyNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 3, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Zachary Freyberg Michael J. McCarthy Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
description	Abstract Antipsychotic drugs are widely prescribed medications, used for numerous psychiatric illnesses. However, antipsychotic drugs cause serious metabolic side effects that can lead to substantial weight gain and increased risk for type 2 diabetes. While individual drugs differ, all antipsychotic drugs may cause these important side effects to varying degrees. Given that the single unifying property shared by these medications is blockade of dopamine D2 and D3 receptors, these receptors likely play a role in antipsychotic drug-induced metabolic side effects. Dopamine D2 and dopamine D3 receptors are expressed in brain regions critical for metabolic regulation and appetite. Surprisingly, these receptors are also expressed peripherally in insulin-secreting pancreatic beta cells. By inhibiting glucose-stimulated insulin secretion, dopamine D2 and dopamine D3 receptors are important mediators of pancreatic insulin release. Crucially, antipsychotic drugs disrupt this peripheral metabolic regulatory mechanism. At the same time, disruptions to circadian timing have been increasingly recognized as a risk factor for metabolic disturbance. Reciprocal dopamine and circadian signaling is important for the timing of appetitive/feeding behaviors and insulin release, thereby coordinating cell metabolism with caloric intake. In particular, circadian regulation of dopamine D2 receptor/dopamine D3 receptor signaling may play a critical role in metabolism. Therefore, we propose that antipsychotic drugs’ blockade of dopamine D2 receptor and dopamine D3 receptors in pancreatic beta cells, hypothalamus, and striatum disrupts the cellular timing mechanisms that regulate metabolism. Ultimately, understanding the relationships between the dopamine system and circadian clocks may yield critical new biological insights into mechanisms of antipsychotic drug action, which can then be applied into clinical practice.
format	article
author	Zachary Freyberg Michael J. McCarthy
author_facet	Zachary Freyberg Michael J. McCarthy
author_sort	Zachary Freyberg
title	Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
title_short	Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
title_full	Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
title_fullStr	Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
title_full_unstemmed	Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
title_sort	dopamine d2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b1ff6b62c4e34477b018d828f67cbac8
work_keys_str_mv	AT zacharyfreyberg dopamined2receptorsandthecircadianclockreciprocallymediateantipsychoticdruginducedmetabolicdisturbances AT michaeljmccarthy dopamined2receptorsandthecircadianclockreciprocallymediateantipsychoticdruginducedmetabolicdisturbances
_version_	1718395186446336000

Dopamine D2 receptors and the circadian clock reciprocally mediate antipsychotic drug-induced metabolic disturbances

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