title: Developmental fluoxetine exposure normalizes the long-term effects of maternal stress on post-operative pain in Sprague-Dawley rat offspring.
abstract: 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.
authors: Department of Anesthesiology/Pain Management, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Liesbeth
authors: L
authors: Knaepen
authors: Ine
authors: I
authors: Rayen
authors: Thierry D
authors: TD
authors: Charlier
authors: Marianne
authors: M
authors: Fillet
authors: Virginie
authors: V
authors: Houbart
authors: Maarten
authors: M
authors: van Kleef
authors: Harry W
authors: HW
authors: Steinbusch
authors: Jacob
authors: J
authors: Patijn
authors: Dick
authors: D
authors: Tibboel
authors: Elbert A
authors: EA
authors: Joosten
authors: Jodi L
authors: JL
authors: Pawluski
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D059225:Nociception / Q000187:drug effects*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000378:metabolism / Q000517:prevention & control*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013312:Stress, Physiological / Q000187:drug effects; D013995:Time; D014156:Transcortin / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014156:Transcortin; C534936:Serpina6 protein, rat