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Fluoxetine Augments the Hypercapnic Ventilatory Response in CO2‐insensitive Brown Norway (BN) Rats
Author(s) -
Puissant Madeleine M,
Mouradian Gary Charles,
Echert Ashley,
Forster Hubert Vincent,
Hodges Matthew R
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb792
Subject(s) - fluoxetine , saline , serotonin , medicine , reuptake inhibitor , anesthesia , ventilation (architecture) , hypercapnia , endocrinology , respiratory system , mechanical engineering , receptor , engineering
The Brown Norway (BN) rat has a severely reduced hypercapnic ventilatory response (HCVR), potentially due to dysfunctional mechanisms of CO 2 /H + chemoreception. BN rats also show reduced brain serotonin (5‐HT), dopamine, and norepinephrine, despite equal numbers of 5‐HT and catecholaminergic neurons. Here, we tested if daily treatment with a selective serotonin reuptake inhibitor (SSRI) fluoxetine (10 mg/kg/day) would augment the blunted HCVR in BN rats. We measured ventilation during room air (RA) and 7% CO 2 breathing in young (age 3 weeks; n=10) and older (age 7 weeks; n=10) BN rats 2 days before and at multiple time points (3, 9, 14 and 21 days) during daily treatment with either fluoxetine (n=6, 6) or saline (n=4, 4). We found no differences in RA breathing or the HCVR (expressed as % room air breathing) prior to treatment, and found no effects of saline treatment at any time points during the experiment. Fluoxetine injections in young and old BN rats increased the HCVR by day 3 of treatment and remained elevated (30–60%) throughout treatment. The older BN group was also studied after discontinuing treatment, where the HCVR remained elevated up to day 3 of withdrawal, after which the HCVR was not different from the saline injected group. Thus, daily SSRI treatment reversibly augments the HCVR in CO 2 ‐insensitive BN rats at multiple ages, further suggesting inherent 5‐HT system dysfunction in the BN rat. Supported by NHLBI HL 097033 .