Chronic blockade of 5‐HT and NE reuptake alters the timing and patterning of phrenic nerve discharge during eupnea, but not gasping, in arterially‐perfused adult mouse

Abstract

Previous in vivo and in vitro studies have demonstrated that a long‐term increase in either 5‐HT or NE exerts complex modulatory effects on central respiratory neural control, resulting in a depression of respiratory motor output. The influence of excess endogenous 5‐HT and NE chronically on respiratory motor output, however, requires clarification. Therefore, in an arterially‐perfused adult mouse preparation, we examined phrenic nerve discharge following intraperitoneal (ip) administration for 28‐d of the 5‐HT and NE reuptake inhibitor venlafaxine hydrochloride (VHCL). The results from these experiments were compared with those obtained from a separate group of mice that received ip injections of 0.9% NaCl (vehicle). We found that in mice receiving VHCL, basal phrenic burst frequency was slower by ~45% (P<0.05), with the effects on TI and TE being somewhat variable. Further, post‐inspiratory activity and spurious expiratory bursts were noted. In response to hypoxia/ischemia, we found that both groups exhibited similar acute hypoxic ventilatory responses and ischemia‐induced gasping responses, with gasps exhibiting similar timing and patterning characteristics. These results demonstrate that chronic excess endogenous 5‐HT and NE depress basal respiratory motor output, but exert minimal effects on hypoxic responses. Supported by NS045321