CHOLINERGIC-OPIOID INTERACTIONS AT BRAIN-STEM RESPIRATORY CHEMOSENSITIVE AREAS IN CATS

Central respiratory chemosensitivity has been ascribed to CO2-sensitiv e neurons located on the ventral brainstem surface. The effects of cho linergic mechanisms of CO2-sensitive neuronal activity recorded extrac ellularly at the brainstem respiratory chemosensitive area at the caud al ventral medullary surface (cVMS) were investigated in cats (n=14) a nesthetized with chloraloseurethane. The neurons increased their firin g rate from 10.4+/-1.6 Hz to 33.9+/-5.2 Hz when the mock cerebrospinal fluid (mCSF) superfusing buffer solution was changed from pH 7.4 (con trol) to pH 7.0 (acidic). Atropine (ATR) applied topically to the cVMS depressed the H+-ion-induced increase in neuronal frequency from 32.8 +/-4.8 Hz to 13.4+/-2.2 Hz. ATR also depressed the inspired-CO2-induce d increase in neuronal activity from 33.2+/-8.3 Hz to 18.9+/-4.9 Hz, s uggesting the possibility of a muscarinic cholinergic involvement in c VMS neuronal responses to changes in PCO2 and mCSF-pH. Acetylcholine ( ACh) increased the activity of cVMS CO2-sensitive neurons by 237.5%+/- 34.9%, and naloxone applied topically to the cVMS augmented the ACh re sponsiveness to 338.6%+/-52.7%. Physostigmine (PHY) increased neuronal activity by 254.3%+/-42.9%, and this increase was augmented to 435.4% +/-61.2% by naloxone. Although responses of the CO2-sensitive neurons to PHY were biphasic, the depressant phase failed to appear whenever t he cVMS was pretreated with naloxone. Naloxone also augmented the resp onsiveness of cVMS neurons to increased H+ ion superfusion. These find ings suggested that the endogenous opiates may be involved in the cent ral regulation of respiration by interaction with CO2-sensitive cholin ergic structures at the cVMS. The cVMS may be a central nervous system site where cholinergic-opioid interactions may be involved in cardior espiratory failure associated with anti-ChE toxicity. (C) 1993 Intox P ress, Inc.