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

Grant number: 21/04119-9
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2021
Effective date (End): January 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Arielle Cristina Arena
Grantee:Lívia Trippe Nagaoka
Host 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 commonly diagnosed neuropsychiatric disorders in school-age children and adolescents, in which catecholamine neurotransmission is impaired, thus pharmacological treatment aims to increase levels of neurotransmitters through psychostimulants. Amongst the most used drugs is Lisdexamfetamine Dimesylate (LDX), a prodrug of dextroamphetamine (D-AMP), that, despite its benefits, can compromise gonadal function and the regulation of various hormonal pathways due to its effect on neurotransmitters levels (DA and NA), possibly causing damage to the male reproductive function. Given the mechanism of action of LDX and its consequences for reproductive function, the customary prescription of this drug is worrisome. This project aims to evaluate the effects of Lisdexamfetamine exposure during the juvenile period and peripuberty on the reproductive parameters of male rats in adulthood. For this, 40 male Wistar rats (DPN 23) will be distributed in 4 experimental groups: a control group (deionized water) and 3 groups of different LDX doses (5.2, 8.6, and 12.1 mg/kg), treatment will occur in 31 consecutive days (DPN 23 to 53). Signs of toxicity and puberty onset will be evaluated during the treatment period, as well as sexual behavior, fertility, and spermatic parameters in adulthood.(AU)

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