Expiratory motor responses to microinjection of D, L homocysteic acid (DLH) in the region of the caudal ventral respiratory column (VRC) are suppressed by intra‐arterial codeine

Abstract

Codeine acts in the brainstem to suppress cough, but the sites at which it acts are unknown. Because codeine suppresses abdominal expulsive activity during cough, we hypothesized that this drug could reduce expiratory pre-motor drive mediated by neurons in the region of the caudal VRC. Parasternal and abdominal muscle electromyograms (EMGs) were recorded from 10 anesthetized, spontaneously breathing cats. Codeine (cumulative dose 10, 30, and 100 ug / kg) or vehicle were injected via the vertebral artery. 25–35 nl of DLH (50 mM) was pressure injected into the caudal VRC to elicit increased abdominal muscle EMG activity. In control animals, the abdominal EMG response to DLH injections was not altered by repeated intra-arterial injections of vehicle (p < 0.28). The highest dose of codeine (100 ug/kg, ia) reduced the peak abdominal EMG activity in response to DLH microinjection by 47± 9 %, and this value was significantly different than that observed following saline injection (p < 0.01). Lower doses of codeine had no significant effect on the abdominal muscle EMG response to DLH microinjection into the caudal VRC. Codeine administration also had no significant effect on end-tidal CO2 in these animals. These results show that intra-arterial codeine can inhibit abdominal motor responses to DLH injected into the caudal VRC. The results are consistent with a suppressive effect of this opioid on caudal VRC pre-motor expiratory neurons. Supported by NIH HL 07125.