The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020860 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097603 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Recency memory is altered in cocaine-withdrawn adolescent rats: Implication of cortical mTOR signaling.
Prog Neuropsychopharmacol Biol Psychiatry
December 2023
Department of Pharmacological and Biomolecular Sciences 'Rodolfo Paoletti', Università degli Studi di Milano, Milan 20133, Italy.
In humans, cocaine abuse during adolescence poses a significant risk for developing cognitive deficits later in life. Among the regions responsible for cognitive processes, the medial prefrontal cortex (mPFC) modulates temporal order information via mechanisms involving the mammalian-target of rapamycin (mTOR)-mediated pathway and protein synthesis regulation. Accordingly, our goal was to study the effect of repeated cocaine exposure during both adolescence and adulthood on temporal memory by studying the mTOR pathway in the mPFC.
View Article and Find Full Text PDFNandrolone decanoate and resistance exercise affect prostate morphology and hormone receptor interface in adult rats with implications for the aging process.
Andrology
January 2020
Department of Anatomy, Institute of Biosciences, University of Estadual Paulista (UNESP), Botucatu, SP, Brazil.
Background: Nandrolone decanoate (ND) is an anabolic-androgenic steroid, and its indiscriminate use leads to subclinical alterations in the hypothalamic-pituitary-gonadal axis and androgen-dependent organs.
Objectives: To evaluate the effects of ND, either alone or in combination with resistance exercise (RE), on the levels of sex hormones, converting enzymes, and steroid receptors and the morphology of the ventral prostate (VP) in adult and aged rats.
Methods: Forty Sprague-Dawley adult and aged rats were divided into four groups each, sedentary and trained with and without ND.
The Effect of a Unilateral Orchiectomy before Gonadotoxic Treatment on the Contralateral Testis in Adult and Prepubertal Rats.
PLoS One
June 2017
Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Purpose: Previous studies have shown that the removal of one testis leads to a compensatory mechanism in the contralateral one, but this was species and age dependent. The aim of this study was to check whether this compensation would still occur after the combination of a unilateral orchiectomy and gonadotoxic treatment, since this resembles the clinical situation of patients who have to undergo highly toxic cancer treatment and therefore choose to cryopreserve a testicular biopsy for fertility restoration purposes.
Materials & Methods: Sprague Dawley rats underwent either unilateral orchiectomy, gonadotoxic busulfan treatment, the combination of both or served as fertile control.
Morphometric study of the corpus cavernosum after anabolic androgenic steroid administration in pubertal and adult rats.
Acta Cir Bras
July 2015
Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Purpose: To evaluate the penile morphological modifications of pubertal and adult rats chronically treated with supra-physiological doses of anabolic androgenic steroids.
Methods: Forty-eight male Wistar rats were distributed into four groups: two control groups, 105- and 65-day-old (C105 and C65, respectively) injected with peanut oil (vehicle); and two treated groups, 105- and 65-day-old (T105 and T65, respectively) injected with nandrolone decanoate at a dose of 10 mg Kg-1 of body weight. The rats were injected once a week for eight weeks.
Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis.
Neuroscience
November 2015
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address:
Methylphenidate (MPH) is a widely prescribed stimulant drug for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Its use in this age group raises concerns regarding the potential interference with ongoing neurodevelopmental processes. Particularly the hippocampus is a highly plastic brain region that continues to develop postnatally and is involved in cognition and emotional behavior, functions known to be affected by MPH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!