Melanin‐concentrating hormone regulates the hypercapnic chemoreflex by acting in the lateral hypothalamic area

Rodrigues, Laísa Taís Cabral; Patrone, Luís Gustavo A.; Gargaglioni, Luciane H.; Dias, Mirela Barros

doi:10.1113/ep090318

Cited by 5 publications

(5 citation statements)

References 95 publications

(136 reference statements)

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“…All the injections had a volume of 0.5 μl/side. Doses were selected based on the Ki values provided by manufacturers and used at doses comparable or less concentrated than previously reported for SNAP94847 (Hsiao et al 2012; Rodrigues et al 2022) or TCS1102 (Kokare et al 2006; Sabetghadam et al 2018; Li et al 2021; Liu et al 2022).…”

Section: Methodsmentioning

confidence: 99%

Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

Barretto-de-Souza

Joseph

Lynch

et al. 2023

Preprint

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Rationale: In a social context, individuals are able to detect external information from others and coordinate behavioral responses according to the situation, a phenomenon called social decision-making. Social decision-making is multifaceted, influenced by emotional and motivational factors like stress, sickness and hunger. However, the neurobiological basis for motivational state competition and interaction are not well known. Objective: We investigated possible neural mechanisms through which internal states could shape social behavior in a social affective preference (SAP) test. In the SAP test, experimental rats given a choice to interact with naive or stressed conspecifics exhibit an age-dependent preference to interact with stressed juvenile conspecifics, but avoid stressed adult conspecifics. First, we assessed the effect of hunger on SAP behavior. Behavior in the SAP test requires the insular cortex, which receives input from the hunger-related peptides melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus (LH). This study aimed to evaluate the role of LH and insular MCH and orexin in SAP test. Methods: SAP tests were conducted in rats that were sated, food deprived or allowed 1 h of access to food after 14 h of deprivation (relieved condition). Separate cohorts of sated rats received cannula implants for microinjection of drugs to inhibit the LH or to block or stimulate MCH or orexin receptors in the insula prior to SAP tests or social interaction tests. Results: Food and water deprivation prior to SAP tests with juvenile rats caused a shift in preference away from the stressed rat toward the naive juveniles. Pharmacological inhibition of LH with muscimol (100 ng/side) abolished the preference for the juvenile stressed conspecific, as well as the preference for the adult naive conspecific. The blockade of MCHr1 or orexin receptors in the insular cortex with SNAP94847 (50 µM) or TCS1102 (1 µM), respectively, also abolished the preference for the stressed juvenile conspecific, but only the antagonism of orexin receptors was able to abolish the preference for the adult naive conspecific. Microinjection of increasing doses (50 or 500 nM) of MCH or orexin-A in the insular cortex increased the interaction time in the one-on-one social interactions test with juvenile conspecifics, however only the microinjection of orexin-A increased the interaction time with adult naive conspecifics. Conclusions: Taken together, these results suggest that lateral hypothalamus peptides shape the direction of social approach or avoidance via actions MCH and orexin neurotransmission in the insular cortex.

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Section: Methodsmentioning

confidence: 99%

Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

Barretto-de-Souza

Joseph

Lynch

et al. 2023

Preprint

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“…Therefore, the data provided by Rodrigues et al. (2022) suggest that MCH in the LH exerts an inhibitory modulation of the hypercapnic ventilatory response during the light (inactive) period in rats.…”

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confidence: 95%

“…The work by Rodrigues et al. (2022) on MCH and the hypercapnic ventilatory response shows scientific quality and relevance; however, important questions remain, and their elucidation will require additional state‐of‐the‐art strategies. For example: Would a hierarchic relationship exist among multiple chemosensitive areas in the brain (brainstem and forebrain)? What is the relatioship between mutiple neuromodulators, including MCH, with hypercapnic ventilatory response? Does MCH modulate the breathing response in arousal or energy balance expenditure conditions? Does the MCH1 receptor regulate hypothalamic neurons directly or via effects on local blood flow and tissue CO 2 retention? What are the synaptic inputs to MCH neurons? Do MCH neurons mediate the arousal or aversive effects of hypercapnia? Do MCH neurons contribute to blood pressure regulation?…”

mentioning

confidence: 99%

“…Using standard in vivo respiratory physiologogical approaches, Rodrigues et al. (2022) demonstrate that application of MCH into the LH decreases the hypercapnic ventilatory response during wakefulness and sleep, only in the light period, whereas MCH antagonism elicits the opposite response. Interestingly, the application of MCH or the blockade of MCH1 receptors in the LC did not affect the hypercapnic ventilatory responses.…”

mentioning

confidence: 99%

“…In this issue of Experimental Physiology , Rodrigues et al. (2022) draw to our attention that melanin‐concentrating hormone (MCH) also regulates the ventilatory response to increased levels of CO 2 . Using standard in vivo respiratory physiologogical approaches, Rodrigues et al.…”

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confidence: 99%

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A new neuromodulatory mechanism in the lateral hypothalamus regulating the hypercapnic ventilatory response in conscious rats

Takakura

2022

Experimental Physiology

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Melanin-concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

et al. 2023

View full text Add to dashboard Cite

Rationale: In a social context, individuals are able to detect external information from others and coordinate behavioral responses according to the situation, a phenomenon called social decision-making. Social decision-making is multifaceted, influenced by emotional and motivational factors like stress, sickness and hunger. However, the neurobiological basis for motivational state competition and interaction are not well known. Objective:We investigated possible neural mechanisms through which internal states could shape social behavior in a social affective preference (SAP) test. In the SAP test, experimental rats given a choice to interact with naïve or stressed conspecifics exhibit an age-dependent preference to interact with stressed juvenile conspecifics, but avoid stressed adult conspecifics. First, we assessed the effect of hunger on SAP behavior. Behavior in the SAP test requires the insular cortex, which receives input from the hunger-related peptides melanin-concentrating hormone (MCH) and orexin neurons of the lateral hypothalamus (LH).This study aimed to evaluate the role of LH and insular MCH and orexin in SAP test.Methods: SAP tests were conducted in rats that were sated, food deprived or allowed 1 h of access to food after 14 h of deprivation (relieved condition). Separate cohorts of sated rats received cannula implants for microinjection of drugs to inhibit the LH or to block or stimulate MCH or orexin receptors in the insula prior to SAP tests or social interaction tests.Results: Food and water deprivation prior to SAP tests with juvenile rats caused a shift in preference away from the stressed rat toward the naïve juveniles. Pharmacological inhibition of LH with muscimol (100 ng/side) abolished the preference for the juvenile stressed conspecific, as well as the preference for the adult naïve conspecific. The blockade of MCHr1 or orexin receptors in the insular cortex with SNAP94847 (50µM) or TCS1102 (1µM), respectively, also abolished the preference for the stressed juvenile conspecific, but only the antagonism of orexin receptors was able to abolish the preference for the adult naïve conspecific.Microinjection of increasing doses (50 or 500 nM) of MCH or orexin-A in the insular cortex increased the interaction time in the one-on-one social interactions test with juvenile conspecifics, however only the microinjection of orexin-A increased the interaction time with adult naïve conspecifics. Social Affect and LH Peptides 3Conclusions: Taken together, these results suggest that lateral hypothalamus peptides shape the direction of social approach or avoidance via actions MCH and orexin neurotransmission in the insular cortex.

show abstract

Melanin‐concentrating hormone regulates the hypercapnic chemoreflex by acting in the lateral hypothalamic area

Cited by 5 publications

References 95 publications

Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

Melanin concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

A new neuromodulatory mechanism in the lateral hypothalamus regulating the hypercapnic ventilatory response in conscious rats

Melanin-concentrating hormone and orexin shape social affective behavior via action in the insular cortex of rat

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