Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala

Reproductive physiology, and physical and sexual development of female offspring born to diabetic dams

OBJETIVOS: O objetivo deste estudo foi avaliar o desenvolvimento físico e sexual e a fisiologia reprodutiva de ratas que se desenvolveram em condições hiperglicêmicas in utero e lactação. MATERIAIS E METODOS: Para induzir o diabetes nas ratas, foi utilizada estreptozotocina em dose única via intravenosa antes do acasalamento. A prole feminina foi avaliada por meio dos seguintes parâmetros: o desenvolvimento físico; a idade de abertura vaginal e do primeiro estro, peso e avaliação histológica do útero e ovários; a duração do ciclo estral, o comportamento sexual e a fertilidade após acasalamentos naturais. RESULTADOS: O diabetes materno provocou, na prole feminina, retardo no desenvolvimento físico; diminuição do peso dos ovários e do número de folículos; a performance reprodutiva foi inferior à do grupo controle. CONCLUSÕES: Concluiu-se que a exposição aos meios intrauterino e lactacional hiperglicêmicos provocou retardo no desenvolvimento físico e sexual e prejudicou a fisiologia reprodutiva de ratas.OBJECTIVES: The objective of this study was to evaluate physical and sexual development and reproductive physiology in female rat offspring that developed in hyperglycemia conditions in utero and during lactation. MATERIALS and METHODS: Maternal diabetes was induced in female rats by a single IV injection of streptozotocin before mating. Female offspring development was evaluated by means of the following parameters: physical development; age of vaginal opening and first estrus; weight and histological evaluation of uterus and ovaries; duration of the estrous cycle, sexual behavior, and fertility after natural mating. RESULTS: In the female offspring, maternal diabetes caused delays in initial physical development; diminution in ovary weight and number of follicles; and inferior reproductive performance compared with the control group. CONCLUSIONS: The exposure to hyperglycemia in uterus and during lactation caused delays in physical and sexual development, and affected the reproductive physiology of female rats negatively.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação para o Desenvolvimento da UNESP (FUNDUNESP)Universidade Estadual Paulista Institute of Biosciences Program in Geral and Applied BiologyUnesp Botucatu Medical School Department of Gynecology and ObstetricsInstitute of Biosciences Centro de Assistência ToxicológicaUniversidade Estadual do Oeste do Paraná (UNIOESTE) Center of Biological and Health SciencesUniversidade Estadual de Campinas Institute of BiologyUnesp Institute of Biosciences Department of MorphologyUniversidade Estadual Paulista Institute of Biosciences Program in Geral and Applied BiologyUnesp Botucatu Medical School Department of Gynecology and ObstetricsUnesp Institute of Biosciences Department of MorphologyFAPESP: 04/12948-0FAPESP: 04/15664-2FUNDUNESP: 01089/0