The Ventral Tegmental Area and Nucleus Accumbens as Circadian Oscillators: Implications for Drug Abuse and Substance Use Disorders

Becker‐Krail, Darius D.; Walker, William H.; Nelson, Randy J.

doi:10.3389/fphys.2022.886704

Cited by 26 publications

(19 citation statements)

References 248 publications

(319 reference statements)

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“…Our observation that ACIII cilia length changes within the SCN depending on the light or dark cycle as recently reported in a pre-print, assured us that our analysis could detect broad scale changes in cilia lengths, frequency and localization (Tu, Li et al 2022). It was interesting that we also detected length changes in cilia with both MCHR1 and ACIII in the shell of the nucleus accumbens at different circadian time points (Becker-Krail, Walker et al 2022). This suggests the potential for cilia mediated signaling changes broadly in the brain based on light conditions.…”

Section: Discussionmentioning

confidence: 88%

Physiological Condition Dependent Changes in Ciliary GPCR Localization in the Brain

Brewer

Engle

Bansal

et al. 2022

Preprint

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Primary cilia are small immotile cellular appendages which mediate diverse types of singling and are found on most mammalian cell types including throughout the central nervous system. Cilia are known to localize certain G protein-coupled receptors (GPCRs) and are critical for mediating the signaling of these receptors. Several of these neuronal GPCRs have recognized roles in feeding behavior and energy homeostasis. Heterologous cell line and model systems like C. elegans and Chlamydomonas have implicated both dynamic GPCR cilia localization and cilia length and shape changes as key for signaling. However, it is unclear if mammalian ciliary GPCRs utilize similar mechanisms in vivo and under what physiological conditions these processes may occur. Here, we use the ciliary GPCRs, melanin concentrating hormone receptor 1 (MCHR1) and neuropeptide-Y receptor 2 (NPY2R) as model ciliary receptors to determine if dynamic localization to cilia occurs. We tested physiological conditions in which these GPCRs have been implicated such as feeding behavior, obesity, and circadian rhythm. Cilia were imaged using confocal microscopy and analyzed with a computer assisted approach allowing for unbiased and high throughput analysis of cilia. We analyzed GPCR positive cilia, cilia frequency as well as cilia length and receptor occupancy. Interestingly we observed changes in ciliary length, receptor occupancy, and cilia frequency under different conditions, but no consistent theme across GPCRs or brain nuclei was observed. A better understanding of the subcellular localization dynamics of ciliary GPCRs could reveal unrecognized molecular mechanisms regulating behaviors like feeding.

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Section: Discussionmentioning

confidence: 88%

Physiological Condition Dependent Changes in Ciliary GPCR Localization in the Brain

Brewer

Engle

Bansal

et al. 2022

Preprint

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“…Opioid analgesic requests and self-administration also vary across the day. The functional relationship between the circadian and reward/opioid systems continues to be well-characterized and is therefore less elusive than the nature of circadian rhythms of pain ( Becker-Krail et al, 2022b ). However, the exact underlying mechanisms that drive daily variations in opioid analgesic efficacy are still not entirely understood.…”

Section: Circadian Rhythms Of Opioid Analgesiamentioning

confidence: 99%

The disruptive relationship among circadian rhythms, pain, and opioids

2023

Self Cite

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Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems. Disruption of circadian rhythms can exacerbate pain behavior and modulate opioid processing, and pain and opioids can influence circadian rhythms. This review highlights evidence demonstrating the relationship among the circadian, pain, and opioid systems. Evidence of how disruption of one of these systems can lead to reciprocal disruptions of the other is then reviewed. Finally, we discuss the interconnected nature of these systems to emphasize the importance of their interactions in therapeutic contexts.

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“…Of the nine regions in the adult mammalian brain harboring DA neurons ( Björklund and Dunnett, 2007 ), those in the ventral midbrain appear critical to linking circadian rhythms associated with feeding or other rewarding stimuli ( Schultz, 2016 ). The VTA DA neurons are known to be important for driving rest phase feeding behavior, and the VTA-NAc pathway has been implicated to be an extra-SCN oscillator that is probably responsible for circadian rhythm disruption related drug abuse ( Becker-Krail et al, 2022 ) (discussed further below). However, the entrainment to scheduled feeding has been linked to a different population of DA neurons: those in the lateral portion of the midbrain, termed the substantia nigra (SN), which project to the DS and are best known for their demise during Parkinson’s disease ( Björklund and Dunnett, 2007 ).…”

Section: Food As a Zeitgebermentioning

confidence: 99%

Dopamine systems and biological rhythms: Let’s get a move on

Tang

Assali

Güler

et al. 2022

Front. Integr. Neurosci.

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How dopamine signaling regulates biological rhythms is an area of emerging interest. Here we review experiments focused on delineating dopamine signaling in the suprachiasmatic nucleus, nucleus accumbens, and dorsal striatum to mediate a range of biological rhythms including photoentrainment, activity cycles, rest phase eating of palatable food, diet-induced obesity, and food anticipatory activity. Enthusiasm for causal roles for dopamine in the regulation of circadian rhythms, particularly those associated with food and other rewarding events, is warranted. However, determining that there is rhythmic gene expression in dopamine neurons and target structures does not mean that they are bona fide circadian pacemakers. Given that dopamine has such a profound role in promoting voluntary movements, interpretation of circadian phenotypes associated with locomotor activity must be differentiated at the molecular and behavioral levels. Here we review our current understanding of dopamine signaling in relation to biological rhythms and suggest future experiments that are aimed at teasing apart the roles of dopamine subpopulations and dopamine receptor expressing neurons in causally mediating biological rhythms, particularly in relation to feeding, reward, and activity.

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The Ventral Tegmental Area and Nucleus Accumbens as Circadian Oscillators: Implications for Drug Abuse and Substance Use Disorders

Cited by 26 publications

References 248 publications

Physiological Condition Dependent Changes in Ciliary GPCR Localization in the Brain

Physiological Condition Dependent Changes in Ciliary GPCR Localization in the Brain

The disruptive relationship among circadian rhythms, pain, and opioids

Dopamine systems and biological rhythms: Let’s get a move on

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