EFFECT OF CODEINE ON THE INSPIRATORY AND EXPIRATORY BURST PATTERN DURING FICTIVE COUGH IN CATS

Experiments were conducted to study the effect of the opioid, codeine, on different components of the cough motor pattern. Midcollicular dec erebrate cats were paralyzed and artificially ventilated by a pump tri ggered by the phrenic neurogram. Inspiratory (phrenic) and expiratory (cranial iliohypogastric) neurograms were recorded. Fictive cough was produced by mechanical stimuli applied to the intrathoracic trachea. C odeine (0.03-1.0 mg . kg(-1), i.v.) decreased cough frequency (average number of coughs per stimulus trial), expiratory burst amplitude, and inspiratory burst amplitude in a dose-dependent manner. The maximum r eduction in cough frequency and expiratory amplitude produced by codei ne was 80-90% for both parameters. However, codeine was more potent in reducing cough frequency (ED(50) = 0.1 mg . kg(-1)) than expiratory b urst amplitude (ED(50) = 0.35 mg . kg(-1)). The maximum observed reduc tion of inspiratory burst amplitude elicited by codeine was approximat ely 40%. There was a positive linear relationship between phrenic and cranial iliohypogastric burst amplitudes during fictive cough (r = 0.8 2, P < 0.001). Codeine destabilized the motor pattern during fictive c ough by disrupting this relationship between inspiratory and expirator y burst amplitudes. We conclude: (a) the central pattern generator for cough is functionally organized into a cough frequency generator, an expiratory burst amplitude generator and an inspiratory burst amplitud e generator, each of which have different sensitivities to codeine (b) there exists a specific codeine-sensitive neural mechanism matching t he relative magnitude of central drive to inspiratory and expiratory m otoneurons during cough.