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Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior.

Rationale: Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. Objective: Our goal was to characterize the acute and chronic effect...

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Published in:Psychopharmacology Vol. 239; no. 8; pp. 2457 - 2471
Main Authors: Straathof, Milou, Blezer, Erwin L. A., Smeele, Christel E., van Heijningen, Caroline, van der Toorn, Annette, Buitelaar, Jan K., Glennon, Jeffrey C., Otte, Willem M., Dijkhuizen, Rick M., TACTICS Consortium, Buitelaar, Jan, de Ruiter, Saskia, Naaijen, Jilly, Akkermans, Sophie, Mennes, Maarten, Zwiers, Marcel, Ilbegi, Shahrzad, Hennissen, Leonie, Glennon, Jeffrey, van de Vondervoort, Ilse
Format: Journal Article
Published: Springer Nature Aug2022
Online Access:View this record in EBSCOhost
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      dt: Aug2022
      vid: 239
      iid: 8
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      pub: Springer Nature
      place: New York, New York
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        158036252
        10.1007/s00213-022-06139-z
        158036252
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        atl: Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior.
      aug:
        au:
          Straathof, Milou
          Blezer, Erwin L. A.
          Smeele, Christel E.
          van Heijningen, Caroline
          van der Toorn, Annette
          Buitelaar, Jan K.
          Glennon, Jeffrey C.
          Otte, Willem M.
          Dijkhuizen, Rick M.
          TACTICS Consortium
          Buitelaar, Jan
          de Ruiter, Saskia
          Naaijen, Jilly
          Akkermans, Sophie
          Mennes, Maarten
          Zwiers, Marcel
          Ilbegi, Shahrzad
          Hennissen, Leonie
          Glennon, Jeffrey
          van de Vondervoort, Ilse
        affil: Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht & Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands
      sug:
      ab: Rationale: Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. Objective: Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity. Methods: Juvenile Sprague–Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8). Results: Memantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections. Conclusions: The lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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