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DAMGO increases CO2 sensitivity and disrupts respiratory rhythm and pattern when injected into the pre‐Botzinger Complex (pre‐Botz C) of awake goats

We investigated the ventilatory effects of the mu‐opoiod agonist, DAMGO (1 nM, 500 nL), when injected into the pre‐Botz C area of the intact, awake goat. DAMGO injected unilaterally or bilaterally into the pre‐Botz C area via chronically implanted microtubules did not change pulmonary ventilation (VE), or respiratory rhythm and pattern during eupneic and hypoxic (PaO2 = 35 mmHg) breathing conditions (n = 4/4 goats), but did increase CO2 sensitivity (VE/PaCO2) (n = 4/4). This contrasts to the typical finding that opioid agonists administered globally depress breathing. Indeed, CO2 sensitivity decreased when DAMGO was injected into the raphe or parapyramidal area in a fifth goat. We also found that bilateral injection of DAMGO into the pre‐Botz C periodically disrupts respiratory rhythm and pattern. In one goat breathing 5 and 7% CO2, periods of decreased inspiratory flow and frequency coincided with large, simultaneous diaphragm and abdominal muscle contractions that were 180° out of phase with flow. In a second goat breathing 5 and 7% CO2, periods of phasic abdominal muscle activity were twice the rate of the diaphragm activity. These data likely reflect the in vitro finding that DAMGO depresses inspiratory (I) neurons, disrupting the normal coupling between the pre‐Botz C inspiratory rhythm generator and a rostrally located expiratory rhythm generator. Thus, our results not only provide in vivo evidence for the coupled oscillator concept, but also suggest that pre‐Botz C I neurons can inhibit CO2 sensitivity.