Robust alternative to the righting reflex to assess arousal in rodents

Gao, Sijia; Calderon, Diany Paola

doi:10.1038/s41598-020-77162-3

Cited by 24 publications

(20 citation statements)

References 43 publications

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“…This reflex is dependent on vestibular inputs that sense head movement but lacks cortical involvement. The righting reflex is frequently used in studies evaluating anesthesia reversal, sepsis survival or traumatic brain injuries ( Gao and Calderon, 2020 ). In general, an increased latency to right is associated with decreased arousal or underlying neurological impairment but a decreased latency has not been shown to correlate with any particular pathophysiological condition or stressed anxiety state ( Gao and Calderon, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…The righting reflex is frequently used in studies evaluating anesthesia reversal, sepsis survival or traumatic brain injuries ( Gao and Calderon, 2020 ). In general, an increased latency to right is associated with decreased arousal or underlying neurological impairment but a decreased latency has not been shown to correlate with any particular pathophysiological condition or stressed anxiety state ( Gao and Calderon, 2020 ). Decreased latency to right is unlikely to be linked to a behavioral or neurological impairment but could be secondary to a non-pathological increased arousal state due to cross-fostering in these litters.…”

Section: Discussionmentioning

confidence: 99%

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Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice

Minakova

Sarafinovska

Mikati

et al. 2021

Front. Behav. Neurosci.

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Nationwide, opioid misuse among pregnant women has risen four-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for neonatal abstinence syndrome (NAS). NAS occurs when a fetus exposed to opioids in utero goes into rapid withdrawal after birth. NAS treatment via continued post-natal opioid exposure has been suggested to worsen neurodevelopmental outcomes. We developed a novel model to characterize the impact of in utero and prolonged post-natal oxycodone (Oxy) exposure on early behavior and development. Via subcutaneous pump implanted before breeding, C57BL/6J dams were infused with Oxy at 10 mg/kg/day from conception through pup-weaning. At birth, in utero oxy-exposed pups were either cross-fostered (paired with non-Oxy exposed dams) to model opioid abstinence (in utero Oxy) or reared by their biological dams still receiving Oxy to model continued post-natal opioid exposure (prolonged Oxy). Offspring from vehicle-exposed dams served as cross-fostered (in utero Veh) or biologically reared (prolonged Veh) controls. In utero Oxy exposure resulted in sex-dependent weight reductions and altered spectrotemporal features of isolation-induced ultrasonic vocalization (USV). Meanwhile, prolonged Oxy pups exhibited reduced weight and sex-differential delays in righting reflex. Specifically, prolonged Oxy female offspring exhibited increased latency to righting. Prolonged Oxy pups also showed decreases in number of USV calls and changes to spectrotemporal USV features. Overall, ontogenetic Oxy exposure was associated with impaired attainment of gross and sensorimotor milestones, as well as alterations in communication and affective behaviors, indicating a need for therapeutic interventions. The model developed here will enable studies of withdrawal physiology and opioid-mediated mechanisms underlying these neurodevelopmental deficits.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice

Minakova

Sarafinovska

Mikati

et al. 2021

Front. Behav. Neurosci.

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“…Brie y, the mouse's back was placed on the ground with its abdomen and limbs facing upward. If the mouse could not turn itself over within 30 s, it was considered to have lost its normal righting re ex [28]. The time point at which the righting re ex was lost was de ned as the drunkenness point, and the duration between the rst drink and drunkenness was taken as the alcohol tolerance time.…”

Section: Detection Of Mouse Intoxicationmentioning

confidence: 99%

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption

Jiang

Yan

Yuan

et al. 2021

Preprint

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Alcohol is an essential drug in human life with multiple medical functions, but excessive alcohol intake, even a single episode of binge-drinking, can cause serious damage. Reducing alcohol consumption or absorption is a direct way to alleviate this harm. Alcohol is decomposed successively by alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) in the liver. Many anti-hangover drugs are intended to increase the activity of these two enzymes, which are weakened in many people owing to gene polymorphisms. Here, we produced a high-activity human ADH1B (hADHIB)-expressing probiotic that secreted the hADH1B enzyme to decompose alcohol in the intestinal tract after oral administration. Our results showed that the oral hADHIB-expressing probiotic reduced the absorption of alcohol, prolonged alcohol tolerance time, and shortened the recovery time after drinking. Alongside, fat accumulation in liver and basal structure disorder of small intestine caused by heavy alcohol intake was improved. Therefore, the engineered probiotic has the potential to be prepared as a mate to wine. This study also demonstrated for the first time that alcohol decomposition can be catalyzed by ectopically expressed hADH1B, providing a practical basis for subsequent development of super-biological antidotes that effectively deliver multiple enzymes.

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“…Its simplicity makes it a favored endpoint in studies investigating anesthetic reversal mechanisms ( Solt et al, 2011 ; Wang et al, 2014 ; Pal et al, 2018 ) and anesthetic sensitivity ( McCarren et al, 2013 ). It is worth noting, however, that RORR is intact in decerebrated rats ( Woods, 1964 ) and is dissociable from cortical patterns of wakefulness ( Gao and Calderon, 2020 ). Furthermore, recent evidence suggests that cortical EEG patterns are dissociable from arousal states in rodents ( Pal et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats

Vincent

Zhang

Kato

et al. 2021

Front. Syst. Neurosci.

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As the number of individuals undergoing general anesthesia rises globally, it becomes increasingly important to understand how consciousness and cognition are restored after anesthesia. In rodents, levels of consciousness are traditionally captured by physiological responses such as the return of righting reflex (RORR). However, tracking the recovery of cognitive function is comparatively difficult. Here we use an operant conditioning task, the 5-choice serial reaction time task (5-CSRTT), to measure sustained attention, working memory, and inhibitory control in male and female rats as they recover from the effects of several different clinical anesthetics. In the 5-CSRTT, rats learn to attend to a five-windowed touchscreen for the presentation of a stimulus. Rats are rewarded with food pellets for selecting the correct window within the time limit. During each session we tracked both the proportion of correct (accuracy) and missed (omissions) responses over time. Cognitive recovery trajectories were assessed after isoflurane (2% for 1 h), sevoflurane (3% for 20 min), propofol (10 mg/kg I.V. bolus), ketamine (50 mg/kg I.V. infusion over 10 min), and dexmedetomidine (20 and 35 μg/kg I.V. infusions over 10 min) for up to 3 h following RORR. Rats were classified as having recovered accuracy performance when four of their last five responses were correct, and as having recovered low omission performance when they missed one or fewer of their last five trials. Following isoflurane, sevoflurane, and propofol anesthesia, the majority (63–88%) of rats recovered both accuracy and low omission performance within an hour of RORR. Following ketamine, accuracy performance recovers within 2 h in most (63%) rats, but low omission performance recovers in only a minority (32%) of rats within 3 h. Finally, following either high or low doses of dexmedetomidine, few rats (25–32%) recover accuracy performance, and even fewer (0–13%) recover low omission performance within 3 h. Regardless of the anesthetic, RORR latency is not correlated with 5-CSRTT performance, which suggests that recovery of neurocognitive function cannot be inferred from changes in levels of consciousness. These results demonstrate how operant conditioning tasks can be used to assess real-time recovery of neurocognitive function following different anesthetic regimens.

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Robust alternative to the righting reflex to assess arousal in rodents

Cited by 24 publications

References 43 publications

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice

Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption

Return of the Righting Reflex Does Not Portend Recovery of Cognitive Function in Anesthetized Rats

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