Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats

Adolescence is a sensitive period for the maturation of prefrontal GABAergic circuitry, particularly involving parvalbumin-expressing (PV+) interneurons that regulate excitatory–inhibitory balance and support attentional control. Methylphenidate (MPH), widely prescribed for attention-deficit/hyperac...

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Authors: Pérez Colorado, Antonio, López García, Juan Carlos, Martínez Marín, Reyes, Vargas Romero, Juan Pedro, Díaz Argandoña, Estrella
Format: article
Status:Published version
Publication Date:2026
Country:España
Institution:Universidad de Sevilla (US)
Repository:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::30c8b6486b8a1004c1ce0170dc0ce843
Online Access:https://hdl.handle.net/11441/187183
https://doi.org/10.1016/j.pnpbp.2026.111757
Access Level:Open access
Keyword:Parvalbumin
Adolescence
Methylphenidate
Sustained attention
Prelimbic cortex
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spelling Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in ratsPérez Colorado, AntonioLópez García, Juan CarlosMartínez Marín, ReyesVargas Romero, Juan PedroDíaz Argandoña, EstrellaParvalbuminAdolescenceMethylphenidateSustained attentionPrelimbic cortexAdolescence is a sensitive period for the maturation of prefrontal GABAergic circuitry, particularly involving parvalbumin-expressing (PV+) interneurons that regulate excitatory–inhibitory balance and support attentional control. Methylphenidate (MPH), widely prescribed for attention-deficit/hyperactivity disorder (ADHD, is commonly administered throughout adolescence, yet its long-term impact on PV+ interneuron development remains unclear. Here, we examined whether chronic MPH exposure during distinct adolescent windows (PD35–55, PD42–62, PD49–69) alters PV+ interneuron maturation in the prelimbic (PrL) cortex and produces enduring attentional impairments. Male and female Wistar rats received 5 mg/kg MPH for 20 consecutive days and, in adulthood (PD100), were tested in a sustained attention task (SAT) and its distractor variant (dSAT). MPH exposure produced a reduction in PV+ interneuron density in the PrL, but only treatment during late adolescence (PD49–69) disrupted the normal developmental increase in PV+ cells. This PV+ reduction interneurons was accompanied by persistent deficits in sustained attention, reflected by decreased hit rates and poor recovery under high attentional demand, while correct rejections remained intact. These findings identify late adolescence as a critical vulnerability window in which MPH disrupts prefrontal inhibitory maturation and is associated with altered adult attentional performance, highlighting the importance of developmental timing in psychostimulant exposure.ElsevierPsicología ExperimentalFisiología Médica y BiofísicaAgencia Estatal de Investigación. EspañaMinisterio de Ciencia, Innovación y Universidades (MICIU). EspañaEuropean Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11441/187183https://doi.org/10.1016/j.pnpbp.2026.111757reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésProgress in Neuro- Psychopharmacology & Biological Psychiatry, 147, 111757. PID2019- 110739GB-I00PID2023-149901NB-I00https://doi.org/10.1016/j.pnpbp.2026.111757info:eu-repo/semantics/openAccessoai:dnet:idus________::30c8b6486b8a1004c1ce0170dc0ce8432026-06-17T12:51:07Z
dc.title.none.fl_str_mv Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
title Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
spellingShingle Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
Pérez Colorado, Antonio
Parvalbumin
Adolescence
Methylphenidate
Sustained attention
Prelimbic cortex
title_short Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
title_full Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
title_fullStr Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
title_full_unstemmed Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
title_sort Long-term consequences of adolescent methylphenidate exposure on sustained attention and prelimbic PV+ interneuron maturation in rats
dc.creator.none.fl_str_mv Pérez Colorado, Antonio
López García, Juan Carlos
Martínez Marín, Reyes
Vargas Romero, Juan Pedro
Díaz Argandoña, Estrella
author Pérez Colorado, Antonio
author_facet Pérez Colorado, Antonio
López García, Juan Carlos
Martínez Marín, Reyes
Vargas Romero, Juan Pedro
Díaz Argandoña, Estrella
author_role author
author2 López García, Juan Carlos
Martínez Marín, Reyes
Vargas Romero, Juan Pedro
Díaz Argandoña, Estrella
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Psicología Experimental
Fisiología Médica y Biofísica
Agencia Estatal de Investigación. España
Ministerio de Ciencia, Innovación y Universidades (MICIU). España
European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
dc.subject.none.fl_str_mv Parvalbumin
Adolescence
Methylphenidate
Sustained attention
Prelimbic cortex
topic Parvalbumin
Adolescence
Methylphenidate
Sustained attention
Prelimbic cortex
description Adolescence is a sensitive period for the maturation of prefrontal GABAergic circuitry, particularly involving parvalbumin-expressing (PV+) interneurons that regulate excitatory–inhibitory balance and support attentional control. Methylphenidate (MPH), widely prescribed for attention-deficit/hyperactivity disorder (ADHD, is commonly administered throughout adolescence, yet its long-term impact on PV+ interneuron development remains unclear. Here, we examined whether chronic MPH exposure during distinct adolescent windows (PD35–55, PD42–62, PD49–69) alters PV+ interneuron maturation in the prelimbic (PrL) cortex and produces enduring attentional impairments. Male and female Wistar rats received 5 mg/kg MPH for 20 consecutive days and, in adulthood (PD100), were tested in a sustained attention task (SAT) and its distractor variant (dSAT). MPH exposure produced a reduction in PV+ interneuron density in the PrL, but only treatment during late adolescence (PD49–69) disrupted the normal developmental increase in PV+ cells. This PV+ reduction interneurons was accompanied by persistent deficits in sustained attention, reflected by decreased hit rates and poor recovery under high attentional demand, while correct rejections remained intact. These findings identify late adolescence as a critical vulnerability window in which MPH disrupts prefrontal inhibitory maturation and is associated with altered adult attentional performance, highlighting the importance of developmental timing in psychostimulant exposure.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/187183
https://doi.org/10.1016/j.pnpbp.2026.111757
url https://hdl.handle.net/11441/187183
https://doi.org/10.1016/j.pnpbp.2026.111757
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Progress in Neuro- Psychopharmacology & Biological Psychiatry, 147, 111757.
PID2019- 110739GB-I00
PID2023-149901NB-I00
https://doi.org/10.1016/j.pnpbp.2026.111757
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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