The Effects of Dopamine Receptor Agonists on the Sleep-Wake Cycle

Herrera-Solís, Andrea; Arias-Carrión, Óscar; Sarro-Ramírez, Andrea; Salas-Crisóstomo, Mireille; Murillo-Rodrı́guez, Eric

doi:10.1007/978-3-319-46437-4_3

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…Acute treatment of freely moving rats with PF-6142 resulted in a significant and dose-dependent increase of wakefulness and associated low-amplitude, high frequency electroencephalographic brain oscillations, primarily in the beta and gamma range. This stimulant activity is in line with increased selective activation of D1Rs ( Herrera Solís et al, 2016 ) and is compatible with previous observations showing wake-promoting and EEG desynchronizing action of D1R agonist in normal ( Ongini et al, 1985 ) and in a narcoleptic rodent model. Interestingly, it has also been shown recently that the D1R agonist SKF-38393 successfully alleviated excessive daytime sleepiness and restored REM sleep to baseline values in a macaque monkey model of Parkinson’s disease ( Hyacinthe et al, 2014 ).…”

Section: Discussionsupporting

confidence: 92%

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

et al. 2020

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Selective activation of dopamine D1 receptors remains a promising pro-cognitive therapeutic strategy awaiting robust clinical investigation. PF-6142 is a key example from a recently disclosed novel series of non-catechol agonists and partial agonists of the dopamine D1/5 receptors (D1R) that exhibit pharmacokinetic (PK) properties suitable for oral delivery. Given their reported potential for functionally biased signaling compared to known catechol-based selective agonists, and the promising rodent PK profile of PF-6142, we utilized relevant in vivo assays in male rodents and male and female non-human primates (NHP) to evaluate the pharmacology of this new series. Studies in rodents showed that PF-6142 increased locomotor activity and prefrontal cortex acetylcholine release, increased time spent in wakefulness, and desynchronized the EEG, like known D1R agonists. D1R selectivity of PF-6142 was supported by lack of effect in D1R knock-out mice and blocked response in the presence of the D1R antagonist SCH-23390. Further, PF-6142 improved performance in rodent models of NMDA receptor antagonist-induced cognitive dysfunction, such as MK-801-disrupted paired-pulse facilitation, and ketamine-disrupted working memory performance in the radial arm maze. Similarly, PF-6142 reversed ketamine-induced deficits in NHP performing the spatial delayed recognition task. Of importance, PF-6142 did not alter the efficacy of risperidone in assays predictive of antipsychotic-like effect in rodents including pre-pulse inhibition and conditioned avoidance responding. These data support the continued development of non-catechol based D1R agonists for the treatment of cognitive impairment associated with brain disorders including schizophrenia.

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Section: Discussionsupporting

confidence: 92%

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

et al. 2020

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show abstract

“…Acute treatment of freely moving rats with PF-6142 resulted in a significant and dose-dependent increase of wakefulness and associated low-amplitude, high frequency electroencephalographic brain oscillations, primarily in the beta and gamma range. This stimulant activity is in line with increased selective activation of D1Rs [54] and is compatible with previous observations showing wake-promoting and EEG desynchronizing action of D1R agonist in normal [55] and in a narcoleptic rodent model. Interestingly, it has also been shown recently that the D1R agonist SKF-38393 successfully alleviated excessive daytime sleepiness and restored REM sleep to baseline values in a macaque monkey model of Parkinson's disease [56].…”

Section: Discussionsupporting

confidence: 92%

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

Kozak¹,

Kiss²,

Dlugolensi³

et al. 2020

Updates in Pharmacology

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“…Nevertheless, the exact role of D 2 receptor agonist and antagonists in modulating behavioral states remain controversial37. Alike DAT, these receptors are primarily expressed in the striatum.…”

mentioning

confidence: 99%

Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation

Holst

Müller

Valomon

et al. 2017

Sci Rep

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Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.

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The Effects of Dopamine Receptor Agonists on the Sleep-Wake Cycle

Cited by 3 publications

References 42 publications

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

Characterization of PF-6142, a Novel, Non-Catecholamine Dopamine Receptor D1 Agonist, in Murine and Nonhuman Primate Models of Dopaminergic Activation

Functional Polymorphisms in Dopaminergic Genes Modulate Neurobehavioral and Neurophysiological Consequences of Sleep Deprivation

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