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Pramipexole restores behavioral inhibition in highly impulsive rats through a paradoxical modulation of frontostriatal networks.

Published version
Peer-reviewed

Repository DOI


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Authors

Fouyssac, Maxime 
Vachez, Yvan M 
Cheng, Yifeng 
Dufourd, Thibault 

Abstract

Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3 receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 by in situ hybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modeling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.

Description

Acknowledgements: The authors want to thank Dr Bizhu He for help with structural equation modeling analysis.


Funder: France Parkinson Association


Funder: Agence Nationale de la Recherche (French National Research Agency); doi: https://doi.org/10.13039/501100001665

Keywords

Rats, Male, Animals, Pramipexole, Impulsive Behavior, Dopamine Agonists, Dopamine, RNA, Messenger

Journal Title

Transl Psychiatry

Conference Name

Journal ISSN

2158-3188
2158-3188

Volume Title

14

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (MR/W019647/1)