Melanin-concentrating hormone (MCH) in the median raphe nucleus: Fibers, receptors and cellular effects

Pascovich, Claudia; Lagos, Patricia; Urbanavicius, Jessika; Devera, Andrea; Rivas, Mayda; Costa, Alícia; Hill, Ximena López; Falconi, Atilio; Scorza, Cecilia; Torterolo, Pablo

doi:10.1016/j.peptides.2019.170249

Cited by 10 publications

(9 citation statements)

References 38 publications

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“…Single unit activity in the mPOA was acquired and processed using Spike2 software (Cambridge Electronic Design, UK). Baseline firing of mPOA units was recorded for at least 300 s. Afterward, juxta-cellular HCRT-1 (100 μM, BACHEM, Bubendorf, Switzerland) diluted in sterile saline 0.9 % (or its vehicle) was applied by pressure pulses of 20 PSI for 200 to 300 ms (Devera et al, 2015; Pascovich et al, 2020). EEG signals were amplified (x1000), filtered (0.1–500 Hz), sampled (1024 Hz, 16 bits), acquired, and processed using the Spike2 software.…”

Section: Methodsmentioning

confidence: 99%

“…We used the Mann–Whitney test to compare the firing rate of each neuron during NREMure vs. REMure (windows of 1 to 5 minutes depending on the firing rate of the analyzed neurons). We also compared the firing rate before and after HCRT-1 administration with the same approach (Torterolo et al, 2002; Cabrera et al, 2013; Devera et al, 2015; Pascovich et al, 2020). The population mean between these conditions was analyzed using the Wilcoxon Signed-Rank Test.…”

Section: Methodsmentioning

confidence: 99%

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Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

Rivas

Serantes

Pascovich

et al. 2022

Preprint

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The medial preoptic area (mPOA) undergoes through neuroanatomical changes across the postpartum period, during which its neurons play a critical role in the regulation of maternal behavior. In addition, this area is also crucial for sleep-wake regulation. We have previously shown that hypocretins (HCRT) within the mPOA facilitate active maternal behaviors in postpartum rats, while the blockade of endogenous HCRT in this area promotes nursing and sleep. To explore the mechanisms behind these HCRT actions, we aimed to evaluate the effects of juxta-cellular HCRT-1 administration on mPOA neurons in urethane-anesthetized postpartum and virgin female rats. We recorded mPOA single units and the electroencephalogram (EEG) and applied HCRT-1 juxta-cellular by pressure pulses. Our main results show that the electrophysiological characteristics of the mPOA neurons and their relationship with the EEG of postpartum rats did not differ from virgin rats. Additionally, neurons that respond to HCRT-1 had a slower firing rate than those that did not. In addition, administration of HCRT increased the activity in one group of neurons while decreasing it in another, both in postpartum and virgin rats. The mechanisms by which HCRT modulate functions controlled by the mPOA involve different cell populations.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

Rivas

Serantes

Pascovich

et al. 2022

Preprint

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“…Intracerebroventricular (ICV) injection of MCH peptide in rats resulted in increased time in both non-REM and REM sleep ( Verret et al, 2003 ). More targeted injections into the locus coeruleus (LC) or raphe nuclei led to increases in REM sleep ( Lagos et al, 2009 , 2011a ; Monti et al, 2015 ; Devera et al, 2015 , 2021 ; Pascovich et al, 2020 , 2021 ), likely through actions on noradrenergic and serotonergic neurons, respectively (see below). Microinjection of MCH into the VLPO, a region implicated in generating NREM sleep, selectively enhanced NREM sleep without affecting REM sleep – however, the physiological relevance of this finding is questionable, given the lack of effect on NREM sleep observed in most subsequent studies of the MCH system ( Benedetto et al, 2013 ).…”

Section: The Role Of the Melanin-concentrating Hormone System In Sleepmentioning

confidence: 99%

The melanin-concentrating hormone system as a target for the treatment of sleep disorders

Potter

Burgess²

2022

Front. Neurosci.

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Given the widespread prevalence of sleep disorders and their impacts on health, it is critical that researchers continue to identify and evaluate novel avenues of treatment. Recently the melanin-concentrating hormone (MCH) system has attracted commercial and scientific interest as a potential target of pharmacotherapy for sleep disorders. This interest emerges from basic scientific research demonstrating a role for MCH in regulating sleep, and particularly REM sleep. In addition to this role in sleep regulation, the MCH system and the MCH receptor 1 (MCHR1) have been implicated in a wide variety of other physiological functions and behaviors, including feeding/metabolism, reward, anxiety, depression, and learning. The basic research literature on sleep and the MCH system, and the history of MCH drug development, provide cause for both skepticism and cautious optimism about the prospects of MCH-targeting drugs in sleep disorders. Extensive efforts have focused on developing MCHR1 antagonists for use in obesity, however, few of these drugs have advanced to clinical trials, and none have gained regulatory approval. Additional basic research will be needed to fully characterize the MCH system’s role in sleep regulation, for example, to fully differentiate between MCH-neuron and peptide/receptor-mediated functions. Additionally, a number of issues relating to drug design will continue to pose a practical challenge for novel pharmacotherapies targeting the MCH system.

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“…We carried out unit recordings using standard procedures with an Ag-Cl electrode inside a glass micropipette of 5-20 MΩ, filled with 2M NaCl; we also handmade fabricated double micropipettes for simultaneous recording and juxta-cellular administration of HCRT (Torterolo et al, 1998;Torterolo et al, 2002;Devera et al, 2015;Pascovich et al, 2020). An Ag-Cl electrode under the neck skin was used as reference for unit recordings.…”

Section: Unit and Eeg Recordingsmentioning

confidence: 99%

“…Baseline firing of mPOA units was recorded for at least 300 s. Afterward, juxta-cellular HCRT-1 (100 µM, BACHEM, Bubendorf, Switzerland) diluted in sterile saline 0.9 % (or its vehicle) was applied by pressure pulses of 20 PSI for 200 to 300 ms (Devera et al, 2015;Pascovich et al, 2020). EEG signals were amplified (x1000), filtered (0.1-500 Hz), sampled (1024 Hz, 16 bits), acquired, and processed using the Spike2 software.…”

Section: Unit and Eeg Recordingsmentioning

confidence: 99%

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

Rivas¹,

Serantes²,

Pascovich³

et al. 2022

Neuroscience Research

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Melanin-concentrating hormone (MCH) in the median raphe nucleus: Fibers, receptors and cellular effects

Cited by 10 publications

References 38 publications

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

The melanin-concentrating hormone system as a target for the treatment of sleep disorders

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

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