Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCA066

Poster Communications

Respiratory changes in rats during postnatal development (P0-26) following prenatal fluoxetine exposure

V. Biancardi1, K. Cardoso Bícego1, L. H. Gargaglioni1

1. Physiology, FCAV/UNESP, Jaboticabal, Brazil.

Serotonin (5-HT) is a neurotransmitter involved in nervous developmental processes, being an important modulator of respiratory rhythm via activation of 5-HT1A and 5-HT2A receptors on respiratory neurons that contribute to hypercapnic and hypoxic ventilatory responses. Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine act as antidepressants and are generally prescribed in depression therapy, including to pregnant women. This study investigated the effects of prenatal (E15-21) exposure to fluoxetine on the ventilatory and metabolic responses to 7% CO2 (hypercapnia) and 10% O2 (hypoxia) of male and female rats during postnatal development (P0-26). To this end, osmotic pumps were implanted subcutaneously in pregnant female rats at embryonic day (E) 15 and delivered vehicle (VEH) or fluoxetine (FLX, 10 mg/Kg/day) during 7 days. Respiratory frequency (fR), ventilation (VE) and O2 consumption (VO2) of pups from these litters were studied. In P0 male rats, the FLX group showed a higher respiratory frequency (fR) in room air conditions [VEH: 95.1±7.0 vs FLX: 130.1±3.8 bpm (breaths per minute)]. There was no difference in the responses to hypercapnia across the two groups, but during hypoxia, VE/VO2 ratio was attenuated in the FLX animals (VEH: 79.2±5.5; FLX: 61.6±6.7). At P6, male FLX animals presented a higher VE/VO2 ratio during hypercapnia (VEH: 56.6±9.3 vs FLX: 79.4±6.5), and an attenuated VE/VO2 ratio during hypoxia (VEH: 96.9±4.5 vs FLX: 78.2±4.1). No differences were observed between male rats in the VEH and FLX groups at P12 and P26. In P0 female rats, FLX animals showed a higher hypercapnic ventilatory response (VEH: 2072.3±196.3 vs FLX: 2521.2±167.0 mL/Kg/min) and higher VE/VO2 ratio (VEH: 45.5±5 vs FLX: 63.0±2.0) but no changes were observed during hypoxia. Fluoxetine-exposed females at P6 showed a higher fR in room air conditions (VEH: 126.7±5.1 bpm vs FLX: 160.9±8.5 bpm), and no differences were observed during hypercapnia and hypoxia across the two groups. At P12, FLX females showed attenuated hypercapnic ventilatory response (VEH: 3549.6±160.3 vs FLX: 2692.8±340.1 mL/Kg/min) and attenuated VE/VO2 ratio (VEH: 97±11.9 vs FLX: 64.8±8.1), but no differences were observed during hypoxia. It is also of note that P26 females displayed a higher VO2 in room air conditions (VEH: 49.8±4.5 vs FLX: 69.8±5.8 mL/Kg/min), and a higher ventilatory response to hypercapnia (VEH: 4695.6±342.7 vs FLX: 5640±290.7 mL/Kg/min). During hypoxia, P26 female FLX animals presented an accentuated VO2 drop (14% for VEH; 22% for FLX) and lower fR (VEH: 175.7±14.5 vs FLX: 152.6±8.5 bpm). Taken together, these data indicate that SSRI exposure during the prenatal period results in long lasting and sex specific changes in the ventilatory and metabolic responses to respiratory challenges.

Where applicable, experiments conform with Society ethical requirements