Acupuncture stimulation at HT7 as a non-pharmacological therapy for sleep disorder caused by caffeine administration in rats

2021 ◽  
pp. 096452842110114
Author(s):  
Su Yeon Seo ◽  
Ji-Young Moon ◽  
Suk-Yun Kang ◽  
O Sang Kwon ◽  
Se Kyun Bang ◽  
...  

Objectives: Insomnia is one of the most common sleep disorders and is difficult to completely treat because of the undesirable side effects of hypnotics. The present study was designed to investigate the hypnotic effect of acupuncture stimulation at HT7 on caffeine-induced sleep disorders and locomotor activity in rats. We also evaluated neuronal activity changes in the arousal region of the basal forebrain. Methods: Rats received intraperitoneal injections of caffeine, and then electroencephalogram power spectrum analysis and locomotor activity measurements were performed. Stimulation at HT7 was performed using a mechanical acupuncture instrument (MAI) before caffeine injection, and its effects on caffeine-induced changes in sleep architecture, locomotor activity and c-Fos expression were examined. Results: Caffeine injection (7.5 mg/kg) produced a significant decrease in slow-wave sleep and an increase in wake time compared with saline injection. Caffeine injection also increased locomotor activity and c-Fos expression in the medial septum–vertical limb of the diagonal band of Broca (MS-VDB), one of the arousal regions of the basal forebrain. Stimulation at HT7 with the MAI alleviated the caffeine-induced sleep disturbance and the increase in locomotor activity. In addition, MAI treatment at HT7, compared with treatment at a location not corresponding to any traditional acupuncture point, reduced the caffeine-induced increase in c-Fos expression. Conclusion: These results indicate that the hypnotic effect of HT7 acupuncture stimulation on caffeine-induced insomnia was associated with suppression of neuronal activity in the basal forebrain.

2021 ◽  
Vol 13 ◽  
Author(s):  
Gabriel Natan Pires ◽  
Isabela Antunes Ishikura ◽  
Sandra Doria Xavier ◽  
Caetano Petrella ◽  
Ronaldo Delmonte Piovezan ◽  
...  

Since the beginning of the COVID-19 pandemic, older adults have been found to be a highly vulnerable group, with a higher prevalence of severe cases and negative outcomes. Research has focused on the reasons why older adults are at greater risk; Sleep-related factors have been suggested as one possible explanation for this. An individual’s sleep pattern undergoes significant changes over the course of their life. In older adults a specific sleep profile can be observed, one characterized by advanced sleep timing, a morningness preference, longer sleep-onset latency, shorter overall sleep duration, increased sleep fragmentation, reduced slow-wave sleep and, increased wake time after sleep onset. Additionally, an increased prevalence of sleep disorders can be observed, such as obstructive sleep apnea and insomnia. Previous research has already linked sleep disorders (especially sleep apnea) with COVID-19, but few studies have focused specifically on the older population. We believe that the intrinsic sleep patterns of older adults, and the prevalence of sleep disorders in this population, may be important factors that could explain why they are at a greater risk of negative COVID-19 outcomes. In this review, we discuss the relationship between sleep and COVID-19 among older adults, focusing on three different aspects: (1) Sleep-related issues that might increase the likelihood of getting infected by SARS-COV-2; (2) Sleep disturbances that might increase the predisposition to worse COVID-19 prognosis and outcomes; and (3) COVID-19-related aspects affecting community-dwelling older adults, such as social isolation, quarantine, and home confinement, among others, that might impact sleep.


2001 ◽  
Vol 281 (1) ◽  
pp. R170-R175 ◽  
Author(s):  
Alfredo Manfridi ◽  
Dario Brambilla ◽  
Mauro Mancia

There is evidence that GABA plays a major role in sleep regulation. GABAA receptor agonists and different compounds interacting with the GABAA receptor complex, such as barbiturates and benzodiazepines, can interfere with the sleep/wake cycle. On the other hand, there is very little information about the possible role of GABAB receptors in sleep modulation. The nucleus basalis of Meynert (NBM), a cholinergic area in the basal forebrain, plays a pivotal role in the modulation of sleep and wakefulness, and both GABAA and GABABreceptors have been described within the NBM. This study used unilateral infusions in the NBM to determine the effects of 3-hydroxy-5-aminomethylisoxazole hydrobromide (muscimol hydrobromide, a GABAA receptor subtype agonist) and β-(aminomethyl)-4-chlorobenzenepropanoic acid (baclofen, a GABAB receptor subtype agonist) on sleep parameters in freely moving rats by means of polygraphic recordings. Muscimol (0.5 nmol) and baclofen (0.7 nmol) induced an increase in slow-wave sleep and an inhibition of wakefulness. Muscimol, but not baclofen, also caused a decrease in desynchronized sleep parameters. The results reported here indicate that 1) the NBM activation of both GABAA and GABAB receptors influences the sleep/wake cycle, and 2) GABAA but not GABAB receptors are important for desynchronized sleep modulation, suggesting that the two GABAergic receptors play different roles in sleep modulation.


2000 ◽  
Vol 278 (3) ◽  
pp. R620-R627
Author(s):  
Xinzheng Xi ◽  
Linda A. Toth

Peripheral administration of lipopolysaccharide (LPS) is associated with alterations in sleep and the electroencephalogram. To evaluate potential neuronal mechanisms for the somnogenic effects of LPS administration, we used unanesthetized rats to survey the firing patterns of neurons in various regions of rat basal forebrain (BF) and hypothalamus during spontaneous sleep and waking and during the epochs of sleep and waking that occurred after the intraperitoneal administration of LPS. In the brain regions studied, LPS administration was associated with altered firing rates in 39% of the neurons examined. A larger proportion of LPS-responsive units showed vigilance-related alterations in firing rates compared with nonresponsive units. Approximately equal proportions of LPS-responsive neurons showed increased and decreased firing rates after LPS administration, with some units in the lateral preoptic area of the hypothalamus showing particularly robust increases. These findings are consistent with other studies showing vigilance-related changes in neuronal activity in various regions of BF and hypothalamus and further demonstrate that peripheral LPS administration alters neuronal firing rates in these structures during both sleep and waking.


Author(s):  
Otavio Lins ◽  
Michelle Castonguay ◽  
Wayne Dunham ◽  
Sonya Nevsimalova ◽  
Roger Broughton

ABSTRACT:Excessive fragmentary myoclonus during sleep consists of high amounts of brief twitch-like movements occurring asynchronously and asymmetrically in different body areas and has been reported to occur in association with a number of sleep disorders. It was analyzed using a new technique of quantification, the fragmentary myoclonus index (FMI). The FMI exhibited high rates in all stages of sleep but with a somewhat lower frequency in slow wave sleep explaining, as well, a significantly lower rate in the first hour after sleep onset compared to later hours. There was no evidence for greater sleep fragmentation or lighter sleep compared to a matched patient group in whom it had not been noted.


2002 ◽  
Vol 30 (02n03) ◽  
pp. 379-385 ◽  
Author(s):  
Hyangsook Lee ◽  
Hi-Joon Park ◽  
Soon Ae Kim ◽  
Hee Jae Lee ◽  
Mi Ja Kim ◽  
...  

Our previous study with functional magnetic resonance imaging (MRI) demonstrated that acupuncture stimulation of the vision-related acupoint, Bl-67, activates the visual cortex of the human brain. As a further study on the effect of Bl-67 acupuncture stimulation on the visual cortex, we examined c-Fos expression in binocularly deprived rat pups. Binocular deprivation significantly reduced the number of c-Fos-positive cells in the primary visual cortex, compared with that of normal control rat pups. Interestingly, acupuncture stimulation of Bl-67 resulted in a significant increase in the number of c-Fos-positive cells in the primary visual cortex, while acupuncture stimulation of other acupoints less important for visual function had no significant effect on c-Fos expression in the primary visual cortex. The results suggest the possibility of vision-related acupoint (Bl-67) having an influence over the activity of the primary visual cortex.


2021 ◽  
Author(s):  
◽  
Natasha Bukholt

<p>Background: MDMA preferentially releases serotonin (5HT) but following repeated exposure there is a decrease in this MDMA-produced effect. At the same time, some studies suggest an increase in MDMA-produced dopamine (DA) release following repeated exposure. The sensitised DA response is often accompanied by sensitisation of MDMA-produced locomotor activity. Because DAergic mechanisms have been implicated in the positively reinforcing properties of MDMA, these neuroadaptations might be relevant to MDMA self-administration.  Objectives: The main objective of this study was to determine whether MDMA self-administration and non-contingent MDMA exposure differentially affected the development of sensitisation to MDMA-produced hyperactivity. Additionally, the relationship between MDMA-produced hyperactivity and changes in c-fos expression in DA terminal regions was determined.  Methods: Triads of rats were designated ‘master’, ‘yoked MDMA’, or ‘yoked saline’. Lever press responding by the master rat resulted in an intravenous infusion of MDMA for both the master rat and the yoked MDMA rat, as well as an equal infusion of vehicle for the yoked control rat. Daily tests continued until a total of 350 mg/kg MDMA had been self-administered. Three days following the last self-administration session, forward and vertical locomotion produced by MDMA (5.0 mg/kg, i.p) were measured during a 2 hr test. Rats were sacrificed immediately following the behavioural test, and c-fos immunohistochemistry was measured.  Results: Repeated MDMA exposure resulted in sensitised forward and vertical locomotor activity. Sensitisation of the increase in forward locomotion was produced only in rats that self-administered MDMA; non-contingent MDMA administration failed to sensitise this behavioural response. In contrast, sensitisation to MDMA-produced vertical activity was produced following both contingent and non-contingent MDMA exposure. C-fos expression was reduced in ventrolateral, and ventromedial areas of the dorsal striatum, as well as the infralimbic cortex, after MDMA exposure, regardless of whether the exposure was via self-administration or yoked administration. A selective decrease in c-fos expression in the nucleus accumbens (NAc) core and the cingulate cortex was produced by MDMA self-administration. There was a negative correlation between MDMA-produced forward locomotor activity and MDMA-produced c-fos expression in the NAc core, cingulate cortex and infralimbic cortex. A negative correlation between rearing activity and MDMA-produced c-fos expression in the NAc core, NAc shell, cingulate cortex, and infralimbic cortex was also found.  Conclusions: These data provide evidence of behavioural sensitisation as a result of repeated MDMA exposure. Furthermore, MDMA-produced behavioural sensitisation was associated with a decrease in c-fos expression that was evident in the NAc and prefrontal cortex. Finally, region-specific changes in c-fos expression suggest an important role of neuroadaptations in the NAc core and the infralimbic cortex as a consequence of MDMA self-administration.</p>


Rheumatology ◽  
2020 ◽  
Author(s):  
Samantha Locke ◽  
Noosha Yousefpour ◽  
Alfredo Ribeiro-da-Silva

Abstract Objectives Alterations beyond joint inflammation such as changes in dorsal horn (DH) excitability contribute to pain in inflammatory arthritis (IA). More complete understanding of specific underlying mechanisms will be important to define novel targets for the treatment of IA pain. Pre-clinical models are useful, but relevant pain assays are vital for successful clinical translation. For this purpose, a method is presented to assess movement-induced pain-related behaviour changes that was subsequently used to investigate DH disinhibition in IA. Methods IA was induced by intra-articular injection of complete Freund’s adjuvant (CFA) in male rats, and weight distribution was assessed before and after walking on a treadmill. To confirm increased activity in nociception-related pathways, fos expression was assessed in the superficial DH, including in nociceptive neurons, identified by neurokinin 1 (NK1) immunoreactivity, and interneurons. Inhibitory terminal density onto NK1+ neurons was assessed and lastly, a cohort of animals was treated for 3 days with gabapentin. Results At 4 weeks post-CFA, walking reduced weight distribution to the affected joint and increased DH fos expression, including in NK1+ neurons. Neuronal activity in inhibitory cells and inhibitory terminal density on NK1+ neurons were decreased in CFA-treated animals compared with controls. Treatment with gabapentin led to recovered behaviour and DH neuronal activity pattern in CFA-treated animals. Conclusion We describe an assay to assess movement-induced pain-related behaviour changes in a rodent IA model. Furthermore, our results suggest that disinhibition may contribute to pain related to movement in IA.


1993 ◽  
Vol 70 (1) ◽  
pp. 117-127 ◽  
Author(s):  
G. D. Kaufman ◽  
J. H. Anderson ◽  
A. J. Beitz

1. The effects of acute and chronic labyrinthectomies on Fos-defined neuronal activity induced by rotation were determined with the use of quantitative image analysis procedures. Unilateral sodium arsanilate labyrinthectomies (UL) were performed either 24 h (acute) or 2 wk (chronic) before exposure to a 90 min, 2-G centripetal acceleration along the interaural axis that stimulated the intact otolith organs. The results obtained from both acute and chronic UL animals subjected to centripetal acceleration were compared with data obtained from nonrotated UL animals and fully intact, normal animals exposed to centripetal acceleration. Such comparisons allowed the definition of functional projections from the otolith organs of one labyrinth to vestibular related and inferior olivary brain stem nuclei in the rat. 2. The effect of the labyrinthectomy on nonrotated animals was first assessed. After acute UL, asymmetric Fos expression was present in the medial and inferior vestibular nuclei, the prepositus hypoglossi (bilaterally), the ipsilateral (with respect to the side of UL) dorsolateral periaqueductal gray, and the contralateral inferior olivary beta subnucleus, as previously described (Kaufman et al., 1992b). Except for minimal labeling in the contralateral prepositus hypoglossi and the dorsolateral periaqueductal gray, the Fos labeling that was present in the brain stem of acute UL animals was absent in chronic UL animals. Thus Fos neuronal activity appears to define a pattern of brain stem activation associated with the initial events that underlie vestibular compensation. 3. In acute UL rats, which were rotated, the contralateral beta subnucleus of the inferior olive had greater labeling (compared with nonrotated UL animals) when the lesion was away from the axis of rotation. In contrast, the ipsilateral beta subnucleus labeled when the lesion was towards the axis of rotation. Fos expression was observed bilaterally in the prepositus hypoglossi when the lesioned side was oriented toward the axis of rotation but was observed only in the contralateral prepositus nucleus when the lesioned side was oriented away from the axis of rotation. Finally, the dorsomedial cell column of the inferior olive (DMCC) was heavily labeled when the lesioned side was oriented towards the axis of rotation but was unlabeled when the lesioned side was oriented away from the axis of rotation. In acute UL nonrotated animals the DMCC was only lightly labeled. All other brain stem nuclear labeling was similar between the acute UL rotated and nonrotated animals.(ABSTRACT TRUNCATED AT 400 WORDS)


2006 ◽  
Vol 24 (3) ◽  
pp. 225-234 ◽  
Author(s):  
Ming Ding ◽  
Linda A. Toth

After influenza infection, C57BL/6J mice develop increased slow-wave sleep (SWS) during the dark phase of the day-night cycle, whereas BALB/cByJ mice develop decreased SWS during the light phase. A previous analysis of CXB recombinant inbred mice revealed a quantitative trait locus (QTL) designated Srilp (sleep response to influenza, light phase) that was related to expression of the BALB/cByJ sleep phenotype. Srilp was localized to the 10- to 12-cM region of mouse Chr 6 between D6Mit74 and D6Mit188. Temt (thioether S-methyltransferase), which is located at region B3 of Chr 6, is a potential candidate gene for Srilp. We evaluated the expression of Temt and other Srilp candidate genes in hypothalamus and basal forebrain of uninfected and influenza-infected C57BL/6J and BALB/cByJ mice. We report here that Temt expression varies significantly with respect to mouse strain, health status, brain region, and day-night phase. C57BL/6J mice show day-night variation in Temt expression in hypothalamus, but BALB/cByJ mice do not. Temt expression in basal forebrain is much higher in C57BL/6J mice than in BALB/cByJ mice. During influenza infection, both C57BL/6J and BALB/cByJ mice show reduced Temt mRNA in basal forebrain at 30 h postinoculation, but expression remains much lower in the BALB/cByJ strain. In contrast, prostaglandin-d-synthase ( Ptgds) and lipocalin 2 ( Lcn2) mRNA increase in basal forebrain of both strains after influenza infection. Administration of the TEMT inhibitor sinefungin reduces sleep in uninfected BALB/cByJ mice and attenuates influenza-induced sleep enhancement in C57BL/6J mice. These data suggest that strain- and infection-related alterations in sleep may be influenced by Temt expression and perhaps by subsequent effects on prostaglandin metabolism.


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