Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

• Published in: PloS one Vol. 8; no. 2; p. e57608
• Main Authors: Knaepen, Liesbeth, Rayen, Ine, Charlier, Thierry D., Fillet, Marianne, Houbart, Virginie, van Kleef, Maarten, Steinbusch, Harry W., Patijn, Jacob, Tibboel, Dick, Joosten, Elbert A., Pawluski, Jodi L.
• Format: Journal Article Web Resource
• Language: English
• Published: United States Public Library of Science 21.02.2013; Public Library of Science (PLoS)
• Subjects: Age Factors; Anesthesia; Anesthesiology; Animals; Animals, Newborn; Antidepressive Agents - pharmacology; Behavior; Biology; Corticosteroids; Dams; Depression (Mood disorder); Depression - drug therapy; Depression - metabolism; Depression/drug therapy/metabolism; Drugs; Exposure; Female; Fluoxetine; Fluoxetine - pharmacology; Gender differences; Gestation; Globulins; Glucocorticoids; Hormones; Human health sciences; Hypersensitivity; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - growth & development; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System/drug effects/growth & development/metabolism; Hypothalamus; Infants; Laboratories; Lactation; Life Sciences; Long-term effects; Mechanical stimuli; Medical research; Medicine; Mental depression; Mental health; Neurosciences; Nociception - drug effects; Offspring; Pain; Pain management; Pain Measurement; Pain perception; Pain, Postoperative - metabolism; Pain, Postoperative - prevention & control; Pain, Postoperative/metabolism/prevention & control; Parturition; Pharmacie, pharmacologie & toxicologie; Pharmacy; Pharmacy, pharmacology & toxicology; Pituitary; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - growth & development; Pituitary-Adrenal System - metabolism; Pituitary-Adrenal System/drug effects/growth & development/metabolism; Postoperative pain; Postoperative period; Pregnancy; Prenatal experience; Rats; Rats, Sprague-Dawley; Rodents; Sciences de la santé humaine; Serotonin; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacology; Social and Behavioral Sciences; Spinal cord; Stress, Physiological - drug effects; Stresses; Studies; Surgery; Time; Transcortin - metabolism; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0057608

Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system.