Investigation of reproductive parameters in male rats exposed to the psychostimulant Lysdexamphetamine from the juvenile period to peripuberty

• Grant number: 21/02225-6
• Support type: Scholarships in Brazil - Master
• Effective date (Start): October 01, 2021
• Effective date (End): February 28, 2023
• Field of knowledge: Interdisciplinary Subjects
• Principal researcher: Arielle Cristina Arena
• Grantee: Julia Stein
• Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Attention deficit hyperactivity disorder (ADHD) is one of the most diagnosed neuropsychiatric disorders in school-age children and adolescents. Studies show that catecholamine neurotransmission is impaired in the brain of these patients, and therefore, pharmacological treatment aims to increase the levels of these neurotransmitters through the use of psychostimulants. For having a more consistent coverage and without the need for repeated administrations throughout the day, long-acting formulations are preferred by most patients. Among the most used drugs is Lysdexamphetamine Dimesylate (LDX), a prodrug of dextroamphetamine (D-AMF), available in the pharmaceutical presentation of capsules in doses of 30, 50 and 70 mg. Despite the benefits of using LDX, its effect on the levels of neurotransmitters can compromise the regulation of several hormonal pathways, and consequently, affect the reproductive system of these individuals. In addition, gonads are subject to regulatory influences by neurotransmitters derived from local synaptic innervation or brought on by adrenal circulation, and changes in these levels can result in impaired reproductive function. Given the mechanism of action of LDX and its consequences for reproductive function, the fact that this drug is highly prescribed for the pediatric age group (6 to 18 years) is worrying. This project aims to evaluate the effects of exposure to Lisdexamphetamine during the juvenile period to peripuberty on reproductive parameters of male rats in adulthood. For that, male Wistar rats (n = 40; 23 days of age) will be used, distributed in 4 groups: Control (deionized water); and three groups that will receive three different doses of Lysdexamphetamine (5.2; 8.6 or 12.1 mg/kg/day). The treatment will occur for 31 consecutive days, orally (gavage). Clinical signs of toxicity, puberty onset and play behavior of these animals during treatment will be evaluated. In adulthood (PND 90) fertility, sexual behavior, hematological parameters, hormonal dosage, sperm parameters, histological analysis, oxidative stress and In Vitro Contraction of vas deferens will be evaluated.