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Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats

Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats
Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats
Background: Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model.

Methods: We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards.


Results: This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose.

Conclusions: This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy.
dopamine, methylphenidate, motivation, prenatal, rat sucrose
1461-1457
pyu044
Lepelletier, F.-X.
4de5b447-1aae-43f5-a5ac-a028dd8441e6
Tauber, C.
d0deb179-ac58-4b57-aed0-08c4b15cd0e3
Nicolas, C.
c8b3c391-bd92-4095-af8d-dbbb79a2119c
Solinas, M.
41892dc6-2e1b-4646-ba30-f60575342924
Castelnau, P.
e2092a25-106d-4ea4-9184-5bffe55615ec
Belzung, C.
acc865ca-d95f-4946-aa8f-44932f0d89d4
Emond, P.
879c1570-18c1-40db-9fc2-62feb04eaebd
Cortese, S.
53d4bf2c-4e0e-4c77-9385-218350560fdb
Faraone, S. V.
60d855ed-a8a8-4eca-9e62-965eb021b1e2
Chalon, S.
5a7bef2b-dfff-4d97-8155-9048f02d7446
Galineau, L.
297e8223-dd15-4291-bb24-1387a9ad0553
Lepelletier, F.-X.
4de5b447-1aae-43f5-a5ac-a028dd8441e6
Tauber, C.
d0deb179-ac58-4b57-aed0-08c4b15cd0e3
Nicolas, C.
c8b3c391-bd92-4095-af8d-dbbb79a2119c
Solinas, M.
41892dc6-2e1b-4646-ba30-f60575342924
Castelnau, P.
e2092a25-106d-4ea4-9184-5bffe55615ec
Belzung, C.
acc865ca-d95f-4946-aa8f-44932f0d89d4
Emond, P.
879c1570-18c1-40db-9fc2-62feb04eaebd
Cortese, S.
53d4bf2c-4e0e-4c77-9385-218350560fdb
Faraone, S. V.
60d855ed-a8a8-4eca-9e62-965eb021b1e2
Chalon, S.
5a7bef2b-dfff-4d97-8155-9048f02d7446
Galineau, L.
297e8223-dd15-4291-bb24-1387a9ad0553

Lepelletier, F.-X., Tauber, C., Nicolas, C., Solinas, M., Castelnau, P., Belzung, C., Emond, P., Cortese, S., Faraone, S. V., Chalon, S. and Galineau, L. (2015) Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats. International Journal of Neuropsychopharmacology, 18 (4), pyu044. (doi:10.1093/ijnp/pyu044).

Record type: Article

Abstract

Background: Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model.

Methods: We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards.


Results: This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose.

Conclusions: This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy.

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More information

e-pub ahead of print date: 31 October 2014
Published date: 2015
Keywords: dopamine, methylphenidate, motivation, prenatal, rat sucrose
Organisations: Clinical Neuroscience

Identifiers

Local EPrints ID: 380160
URI: http://eprints.soton.ac.uk/id/eprint/380160
ISSN: 1461-1457
PURE UUID: 14004013-834d-4d91-9c7d-41524d38a4ab
ORCID for S. Cortese: ORCID iD orcid.org/0000-0001-5877-8075

Catalogue record

Date deposited: 19 Aug 2015 16:05
Last modified: 15 Mar 2024 03:52

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Contributors

Author: F.-X. Lepelletier
Author: C. Tauber
Author: C. Nicolas
Author: M. Solinas
Author: P. Castelnau
Author: C. Belzung
Author: P. Emond
Author: S. Cortese ORCID iD
Author: S. V. Faraone
Author: S. Chalon
Author: L. Galineau

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