TY - JOUR
T1 - Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior
AU - TACTICS Consortium
AU - Straathof, Milou
AU - Blezer, Erwin L.A.
AU - Smeele, Christel E.
AU - van Heijningen, Caroline
AU - van der Toorn, Annette
AU - Buitelaar, Jan K.
AU - Glennon, Jeffrey C.
AU - Otte, Willem M.
AU - Dijkhuizen, Rick M.
AU - de Ruiter, Saskia
AU - Naaijen, Jilly
AU - Akkermans, Sophie
AU - Mennes, Maarten
AU - Zwiers, Marcel
AU - Ilbegi, Shahrzad
AU - Hennissen, Leonie
AU - Glennon, Jeffrey
AU - van de Vondervoort, Ilse
AU - Kapusta, Katarzyna
AU - Bielczyk, Natalia
AU - Amiri, Houshang
AU - Havenith, Martha
AU - Franke, Barbara
AU - Poelmans, Geert
AU - Bralten, Janita
AU - Heskes, Tom
AU - Sokolova, Elena
AU - Groot, Perry
AU - Williams, Steven
AU - Murphy, Declan
AU - Lythgoe, David
AU - Bruchhage, Muriel
AU - Dud, Iulia
AU - Voinescu, Bogdan
AU - Dittmann, Ralf
AU - Banaschewski, Tobias
AU - Brandeis, Daniel
AU - Mechler, Konstantin
AU - Berg, Ruth
AU - Wolf, Isabella
AU - Häge, Alexander
AU - Landauer, Michael
AU - Hohmann, Sarah
AU - Boecker-Schlier, Regina
AU - Ruff, Matthias
AU - Dijkhuizen, Rick
AU - Blezer, Erwin
AU - Straathof, Milou
AU - van der Marel, Kajo
AU - Joel, Daphna
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
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.
KW - Compulsive behavior
KW - Diffusion magnetic resonance imaging
KW - Frontostriatal circuitry
KW - Functional magnetic resonance imaging
KW - NMDA antagonist
UR - http://www.scopus.com/inward/record.url?scp=85134350290&partnerID=8YFLogxK
U2 - 10.1007/s00213-022-06139-z
DO - 10.1007/s00213-022-06139-z
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C2 - 35419637
AN - SCOPUS:85134350290
SN - 0033-3158
VL - 239
SP - 2457
EP - 2470
JO - Psychopharmacology
JF - Psychopharmacology
IS - 8
ER -