Attenuation of drug-induced loss of righting reflex response by pretreatment with a nitric oxide donor

Background/Aims: The role of nitric oxide (NO) in general anesthetic drug action is controversial. The present study was carried out to determine the role of NO in the loss of righting reflex induced by injectable sedative and anesthetic drugs. Methods: Under isoflurane anesthesia, male NIH Swiss mice received an intracerebroventricular microinjection of the NOdonor 3-morpholinosydnoimine (SIN-1) 30 min prior to an i.p. injection of chloral hydrate, sodium barbital, midazolam or ketamine/xylazine. Mice were monitored for onset and duration of loss of righting reflex (LORR). Results: Pretreatment with SIN-1 reduced the mean duration of LORR induced by chloral hydrate, sodium barbital and midazolam but not ketamine/xylazine. Pretreatment with SIN-1 had no effect on the mean latency to LORR. Conclusion: It is concluded that there may be a differential involvement of NO in the LORR response, depending upon whether the primary drug action is through GABA_A or NMDA receptors.