, Volume 233, Issue 4, pp 727–737 | Cite as

Inhibition of hippocampal plasticity in rats performing contrafreeloading for water under repeated administrations of pramipexole

  • Chiara Schepisi
  • Annabella Pignataro
  • Salvatore Simone Doronzio
  • Sonia Piccinin
  • Caterina Ferraina
  • Silvia Di Prisco
  • Marco Feligioni
  • Anna Pittaluga
  • Nicola Biagio Mercuri
  • Martine Ammassari-Teule
  • Robert Nisticò
  • Paolo Nencini
Original Investigation



Compulsive symptoms develop in patients exposed to pramipexole (PPX), a dopaminergic agonist with high selectivity for the D3 receptor. Consistently, we demonstrated that PPX produces an exaggerated increase in contrafreeloading (CFL) for water, a repetitive and highly inflexible behavior that models core aspects of compulsive disorders.


Given the role of the hippocampus in behavioral flexibility, motivational control, and visuospatial working memory, we investigated the role of hippocampus in the expression of PPX-induced CFL. To this aim, rats were subjected to CFL under chronic PPX, and then examined for the electrophysiological, structural, and molecular properties of their hippocampus.


We measured long-term potentiation (LTP) at CA1 Schaffer collaterals, dendritic spine density in CA1 pyramidal neurons, and then glutamate release and expression of pre and postsynaptic proteins in hippocampal synaptosomes. The effects of PPX on hippocampal-dependent working memory were assessed through the novel object recognition (NOR) test.


We found that PPX-treated rats showing CFL exhibited a significant decrease in hippocampal LTP and failed to exhibit the expected increase in hippocampal spine density. Glutamate release and PSD-95 expression were decreased, while pSYN expression was increased in hippocampal synaptosomes of PPX-treated rats showing CFL. Despite a general impairment of hippocampal synaptic function, working memory was unaffected by PPX treatment.


Our findings demonstrate that chronic PPX affects synaptic function in the hippocampus, an area that is critically involved in the expression of flexible, goal-centered behaviors. We suggest that the hippocampus is a promising target in the pharmacotherapy of compulsive disorders.


Pramipexole Contrafreeloading Obsessive-compulsive disorder Hippocampus D3 receptor 


Compliance with ethical standards

Funding and disclosures

This study was funded by intramural grants from Sapienza University. The authors report no biomedical financial interests or potential conflicts of interest.

Supplementary material

213_2015_4150_MOESM1_ESM.doc (40 kb)
Supplementary Materials and Methods (DOC 39 kb)
213_2015_4150_MOESM2_ESM.doc (166 kb)
Figure S1 Chronic systemic treatment with PPX decreases the fraction of water consumed over water gained during the session. Bars represent the average of the: (a) Operant phase . b) Choice phase. Data are expressed as mean ± SEM. *=p<.05 PPX vs VEH. (DOC 165 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Chiara Schepisi
    • 1
  • Annabella Pignataro
    • 2
  • Salvatore Simone Doronzio
    • 1
  • Sonia Piccinin
    • 3
  • Caterina Ferraina
    • 3
  • Silvia Di Prisco
    • 4
  • Marco Feligioni
    • 3
  • Anna Pittaluga
    • 4
  • Nicola Biagio Mercuri
    • 2
  • Martine Ammassari-Teule
    • 2
    • 5
  • Robert Nisticò
    • 1
    • 3
  • Paolo Nencini
    • 1
  1. 1.Department of Physiology and PharmacologySapienza UniversityRomeItaly
  2. 2.IRCCS Santa LuciaRomeItaly
  3. 3.European Brain Research InstituteRomeItaly
  4. 4.Department of Pharmacy, Center of Excellence for Biomedical ResearchUniversity of GenoaGenoaItaly
  5. 5.Institute of Cell Biology and Neurobiology, National Research CouncilRomeItaly

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