MORPhA Scale: behavioral and electroencephalographic validation of a rodent anesthesia scale

Abstract

Degree of anesthesia in laboratory rodents is normally evaluated by testing loss of reflexes. While these are useful endpoint assessments, they are of limited application to study induction/reversal kinetics or factors affecting individual susceptibility (e.g. sex or age). We developed and validated a grading system for a temporal follow up of anesthesia. The Minho Objective Rodent Phenotypical Anesthesia (MORPhA) scale was tested in mice and rats anaesthetized with a mixture of ketamine/dexmedetomidine (ket/dex -3 doses). The scale comprises 12 behavioral readouts organized in 5 stages -(i) normal/(ii) hindered voluntary movement, elicited response to (iii) non-noxious/(iv) noxious stimuli and (v) absence of responseevaluated at regular time points. Progression across stages was monitored by electroencephalography (EEG) in rats during anesthesia induction and reversal (atipamezole) and during induction with a second anesthetic drug (pentobarbital). Higher anesthetic doses decreased the time to reach higher levels of anesthesia during progression, while increasing the time to regain waking behavior during reversal, in mice and in rats. A regular decrease in high frequencies (low and high gamma) power was observed as the MORPhA score increased during anesthesia induction, while the opposite pattern was observed during emergence from anesthesia through reversion of dex effect. The devised anesthetic scale is of simple application and provides a semi-quantifiable readout of anesthesia induction/reversal.

Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

“…Different published methods for monitoring anesthesia in rodents mainly utilize reflexes, such as response to painful stimuli, the righting reflex 5,8,13 and behavioral scales 32,33 . However, they are limited by the inability to assess subjects integrating the qualities that constitute the arousal process 34 .…”

“…However, they are limited by the inability to assess subjects integrating the qualities that constitute the arousal process 34 . The group of Esteves and colleagues 32 created a scale based on objective behavioral changes describing the sequences of motor behaviors during anesthesia induction and emergence. Despite using injected anesthetics (ketamine/dexmedetomidine) to anesthetize mice and atipamezole for emergence, they observed similar behaviors as the ones described here, suggesting that arousal behavior is common among inhaled and injected anesthetics.…”

High trait impulsivity potentiates the effects of chronic pain on impulsive behavior

“…Chronic neuropathic pain was induced using the SNI (Decosterd and Woolf, 2000). Rats were anesthetized via intraperitoneal administration of 1:1.5 mix (1 ml/kg) of Sededorm® (Medetomidine, 1 mg/mL – VetPharma Animal Health, Spain) and Ketamidor® (Ketamine, 100 mg/mL – Richter Pharma AG, Austria), respectively (Esteves et al, 2019). A blunt incision was then performed to expose the three branches of sciatic nerve: common peroneal, tibial and sural nerves.…”