Heart rate variations caused by opioid agonists in the nucleus of the solitary tract of cats are independent of nociception and EEG states

The present study aims to elucidate the involvement of the Nucleus of the Solitary Tract (NST) in opioid-induced heart rate (HR) changes in the absence of nociceptive input across different behavioral states, including wakefulness (W) and slow-wave sleep (SWS), given the clinical significance of the parasympathomimetic effects of opioids. Three adult cats with a stereotactic-guided implanted cannula aimed at the NST and with electrodes for electroencephalogram (EEG), electromyogram (EMG), electrooculogram (EOG) to identify W-SWS states and EKG recordings to obtain RR-intervals were used. After microinjections of saline, morphine sulphate, morphiceptin (mu-agonist), D-pen-2-D-pen-5-enkephalin (delta-agonist), or U-50488H (kappa-agonist) and after morphine preceded by naloxone, 60-min polygraph recordings were obtained “in vivo”. RR-intervals 60 min after NST administration were significantly increased (p < 0.001) after morphine (542 ± 108 ms), mu-agonist (525 ± 102 ms) and delta-agonist (472 ± 70 ms) as compared with saline (429 ± 68 ms), and the three substances also caused an EEG synchronization with a statistically significant increase of time spent in SWS (p < 0.05). These RR-interval changes were also statistically significant during both W (p < 0.015) and SWS states (p < 0.001). All the morphine induced EKG and EEG changes were blocked by prior administration of naloxone. NST injection of kappa-agonist was not followed by any significant effect. Therefore, opioids, by activating the mu and delta opioid receptors located in the NST, directly stimulate the parasympathetic component of HRindependently on EEG-behavioral states and even in the absence of pain.