Inhibition of breathing after stimulation of muscle is mediated by endogenous opiates and GABA.

Stimulation of receptors in hindlimb muscles activates a supraspinal mechanism which causes a prolonged, post-stimulatory depression of breathing (Waldrop, T.G., F.L. Eldridge and D.E. Millhorn, 1982, Respir. Physiol. 50: 239-254). In the present study phrenic nerve responses to stimulation of hindlimb muscles were studied in anesthetized, paralyzed cats whose vagi and carotid sinus nerves had been cut. Body temperature and end-tidal PCO2 were kept constant with servocontrollers. The post-stimulatory depression of breathing was greatly attenuated in cats pretreated with an opiate antagonist (naloxone) and did not occur in animals pretreated with a GABA antagonist (bicuculline). The response was not blocked by prior administration of either a serotonin antagonist (methysergide) or a dopamine and norepinephrine antagonist (alpha-methyltyrosine). We conclude that endogenous opiates and possibly GABA, but not serotonin, dopamine or norepinephrine, are involved in the neural mechanism responsible for the prolonged depression of breathing.