Effect of Sleep Deprivation on Righting Reflex in the Rat Is Partially Reversed by Administration of Adenosine A1 and A2 Receptor Antagonists

Tung, Avery; Herrera, Stacy; Szafran, Martin J.; Kasza, Kristen; Mendelson, Wallace B.

doi:10.1097/00000542-200506000-00015

Cited by 44 publications

(30 citation statements)

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“…In in vitro studies, mefloquine has been shown to interact with a number of potential neurological targets, including neuronal calcium homeostasis, the endoplasmic reticulum calcium pump, acetylcholinesterase, blood-brain barrier P glycoproteins, glutaminergic synaptic activity, connexins, A 2 a receptors, and potassium and anion channels (6,8,16,17,21,22,24,30,44). The A 2 a receptor is a strong candidate for potential involvement, given its suspected role in sleep modulation and its potent inhibition by mefloquine (41,42,44).…”

Section: Discussionmentioning

confidence: 99%

Mefloquine Induces Dose-Related Neurological Effects in a Rat Model

Dow¹,

Bauman²,

Caridha³

et al. 2006

Antimicrob Agents Chemother

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Mefloquine is one of the drugs approved by the FDA for malaria chemoprophylaxis. Mefloquine is also approved for the treatment of malaria and is widely used for this purpose in combination with artesunate. However, the clinical utility of the compound has been compromised by reports of adverse neurological effects in some patients. In the present study, the potential neurological effects of mefloquine were investigated with six 7-week-old female rats given a single oral dose of the compound. Potential mefloquine-induced neurological effects were monitored using a standard functional observational battery, automated open field tests, automated spontaneous activity monitoring, a beam traverse task, and histopathology. Plasma mefloquine concentrations were determined 72 h after dosing by using liquid chromatography-mass spectrometry. Mefloquine induced dose-related changes in endpoints associated with spontaneous activity and impairment of motor function and caused degeneration of specific brain stem nuclei (nucleus gracilis). Increased spontaneous motor activity was observed only during the rats' normal sleeping phase, suggesting a correlate to mefloquine-induced sleep disorders. The threshold dose for many of these effects was 187 mg/kg of body weight. This dose yielded plasma mefloquine concentrations after 72 h that are similar to those observed in humans after the treatment dose. Collectively, these data suggest that there may be a biological basis for some of the clinical neurological effects associated with mefloquine.

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Section: Discussionmentioning

confidence: 99%

Mefloquine Induces Dose-Related Neurological Effects in a Rat Model

Dow¹,

Bauman²,

Caridha³

et al. 2006

Antimicrob Agents Chemother

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“…It is generally considered that the majority of actions ascribed to therapeutic doses of xanthines (caffeine and theophylline) are due to their action as adenosine receptor antagonists [13]. The role of adenosine in sleep and its sedative/hypnotic activities are well known [14][15][16][17][18]. In our volunteer study noted above, we demonstrated the antagonistic actions of aminophylline on propofol sedation; these actions were assessed using both the bispectral index (BIS) and behavioral responses to verbal commands.…”

Section: Discussionmentioning

confidence: 69%

Aminophylline reversal of prolonged postoperative sedation induced by propofol

et al. 2008

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Propofol is frequently used for intravenous sedation or anesthesia in ambulatory and office-based anesthesia. Although awakening is usually rapid, there are instances of delayed recovery from propofol anesthesia. It has been reported that aminophylline antagonizes the sedative effects of several anesthetic and analgesic drugs. The case reports presented here demonstrate that intravenous aminophylline effectively reversed prolonged propofol-induced sedation/anesthesia in the postoperative period. There were no side effects or delayed re-sedation after the administration of aminophylline. Our study suggests that aminophylline could be a clinically useful propofol antagonist.

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“…In rodents, loss of consciousness can be measured by the LoRR and resumption of consciousness can be analyzed by the RoRR (19,20). Fig.…”

Section: Methodsmentioning

confidence: 99%

GABAergic ventrolateral pre-optic nucleus neurons are involved in the mediation of the anesthetic hypnosis induced by propofol

Yuan

Luo

Zhang

et al. 2017

Molecular Medicine Reports

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Intravenous anesthetics have been used clinically to induce unconsciousness for seventeen decades, however the mechanism of anesthetic-induced unconsciousness remains to be fully elucidated. It has previously been demonstrated that anesthetics exert sedative effects by acting on endogenous sleep-arousal circuits. However, few studies focus on the ventrolateral pre-optic (VLPO) to locus coeruleus (LC) sleep-arousal pathway. The present study aimed to investigate if VLPO is involved in unconsciousness induced by propofol. The present study additionally investigated if the inhibitory effect of propofol on LC neurons was mediated by activating VLPO neurons. Microinjection, target lesion and extracellular single-unit recordings were used to study the role of the VLPO-LC pathway in propofol anesthesia. The results demonstrated that GABAA agonist (THIP) or GABAA antagonist (gabazine) microinjections into VLPO altered the time of loss of righting reflex and the time of recovery of righting reflex. Furthermore, propofol suppressed the spontaneous firing activity of LC noradrenergic neurons. There was no significant difference observed in firing activity between VLPO sham lesion and VLPO lesion rats. The findings indicate that VLPO neurons are important in propofol-induced unconsciousness, however are unlikely to contribute to the inhibitory effect of propofol on LC spontaneous firing activity.

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Effect of Sleep Deprivation on Righting Reflex in the Rat Is Partially Reversed by Administration of Adenosine A1 and A2 Receptor Antagonists

Cited by 44 publications

References 0 publications

Mefloquine Induces Dose-Related Neurological Effects in a Rat Model

Mefloquine Induces Dose-Related Neurological Effects in a Rat Model

Aminophylline reversal of prolonged postoperative sedation induced by propofol

GABAergic ventrolateral pre-optic nucleus neurons are involved in the mediation of the anesthetic hypnosis induced by propofol

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