Activation of 5-HT1A receptors in the preBötzinger region has little impact on the respiratory pattern

• Intravenous 5-HT1A receptor agonist 8-OH-DPAT induces brisk tachypnea in dogs.
• Highly localized 8-OH-DPAT depresses preBötzinger region I and E neurons.
• Ventral respiratory column 8-OH-DPAT injections induce no phrenic response.
• Effects of Intravenous 8-OH-DPAT originate outside of the ventral respiratory column.

The preBötzinger (preBötC) complex has been suggested as the primary site where systemically administered selective serotonin agonists have been shown to reduce or prevent opioid-induced depression of breathing. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine whether 5-HT1A receptors within the preBötC and ventral respiratory column (VRC) mediate the tachypneic response induced by intravenous (IV) (±)-8-Hydroxy-2-diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8-OH-DPAT (19 ± 2 μg/kg) reduced both inspiratory (I) and expiratory (E) durations by ∼40%, but had no effect on peak phrenic activity (PPA). Picoejection of 1, 10, and 100 μM 8-OH-DPAT on I and E preBötC neurons produced dose-dependent decreases up to ∼40% in peak discharge. Surprisingly, microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm rostral had no effect on timing and PPA. These results suggest that the tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the areas we studied.