[18F]-FDG PET neuroimaging in rats with quinpirole-induced checking behavior as a model for obsessive compulsive disorder

Servaes, Stijn; Glorie, Dorien; Verhaeghe, Jeroen; wyffels, Leonie; Stroobants, Sigrid; Staelens, Steven

doi:10.1016/j.pscychresns.2016.10.003

Cited by 11 publications

(10 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Model setup was successful as shown by the results from the OFT. Animals from the QP group showed excessive checking behaviour when compared to animals from the SAL group (Fig 2), that gets progressively worse with continuous exposure to QP (Fig 1), in correspondence to earlier studies using the same model [17,28]. Consistent with expectations, control animals show the most activity during the first fifteen minutes in the behavioural cage.…”

Section: Discussionsupporting

confidence: 90%

“…The research that followed on these findings mainly focused on the behavioural side for pharmacological validation of certain drugs or treatments [25–27]. Previous work of our group has established the effects of repeated exposure to QP and the open field with molecular imaging of both the glucose metabolism [28], as well as dopamine (DA) receptor occupancy and metabotropic glutamate 5 receptor (mGluR5) distribution [17]. This has led us to design the current study to validate the previous DA and mGluR5 results in the QP model with ex-vivo immunohistochemistry extending it with the glutamate transporter 1 (GLT-1), in order to determine whether the differences are indeed a consequence of receptor downregulation or internalisation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neuroreceptor kinetics in rats repeatedly exposed to quinpirole as a model for OCD

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background Obsessive-compulsive disorder (OCD) is a chronic, incapacitating, early onset psychiatric disorder that is characterized by obsessions and compulsions originating from a disturbance in the cortico-striato-thalamico-cortical circuit. We implemented the preclinical quinpirole (QP) rat model for compulsive checking in OCD to analyse the behaviour and visualize the D2R, mGluR5 and GLT1 density in order to contribute to the understanding of the neuroreceptor kinetics. Methods Animals (n = 14) were exposed to either saline (1 mL/kg) or QP (dopamine D2-agonist, 0.5 mg/kg) twice-weekly during 7 weeks. After each injection animals were placed on an open field test. After model setup, animals were placed in a behavioural cage equipped with tracking software and hardware in order to analyse the behaviour. Subsequently, sagittal slides were made of the CP in the right hemisphere and a staining was done with the D2R, mGluR5 and GLT-1 antibody to visualize the corresponding receptor. Results The QP animals displayed a strong increase in travelled distance (+596.70%) and in the number of homebase visits (+1222.90%) compared to the control animals. After chronic exposure to QP, animals had a significantly (p < 0.05) higher percentage of D2R density in the CP (7.92% ± 0.48%) versus 6.66% ± 0.28% in animals treated with saline. There were no differences for mGluR5 and GLT1 receptor density. Conclusions Chronic exposure to QP leads to hyperlocomotion and an increase in D2R density. Furthermore, as mGluR5 and GLT1 density did not seem to be directly affected, decreased levels of glutamate might have influenced the binding potential in earlier reports.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Neuroreceptor kinetics in rats repeatedly exposed to quinpirole as a model for OCD

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…Serveas et al showed that acute treatment of rats with the dopamine D 2/3 receptor agonist quinpirole provoked a global increase in [ 18 F]FDG whole-brain uptake, yet a relatively lower increase in NAc, DS, and the frontal cortical regions, i.e. mPFC, ACC and OFC (73) , suggesting a common mechanism. Global increased [ 18 F]FDG uptake can hide regional differences in metabolism, emphasizing the importance of whole-brain normalization between baseline and condition (75) .…”

Section: Discussionmentioning

confidence: 99%

“…Metabolic mapping of [ 18 F]FDG uptake by PET can identify neuronal circuits related to behavior, chemical stimulation or chemogenetic-induced circuit modulation (53,54,(70)(71)(72)(73). We evaluated the whole-brain normalized [ 18 F]FDG uptake in a fasting condition (74).…”

Section: Nigro-striatal Dopaminergic Stimulation Affects Metabolic Fumentioning

confidence: 99%

Dorsal striatal dopamine induces fronto-cortical hypoactivity and implies reduced anxiety and compulsive behaviors in rats

Casado-Sainz

Gudmundsen

Bærentzen

et al. 2021

Preprint

View full text Add to dashboard Cite

Nigro-striatal dopamine transmission in the rat dorsomedial striatum (DMS) engages the cortico-striato-thalamo-cortical (CSTC) circuit. Modulation of the CSTC circuit can emulate behavioral and functional aspects of neuropsychiatric diseases, including obsessive compulsive disorder (OCD). Classical pharmacological and neurotoxic manipulations of brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations. In this study, we developed a chemogenetic method for selective activation of dopamine neurons innervating the rat DMS, and used this approach to investigate effects of targeted dopamine activation on CSTC circuit function. We monitored behavioral effects on locomotion, self-grooming, and prepulse inhibition of the startle response, which are stereotypic behaviors related to OCD, as well as effects on metabolic functional connectivity measured by [18F]FDG PET, and regional concentrations of neurochemicals (i.e., glutamate, glutamine, N-acetylaspartate and N-acetylaspartateglutamate) measured by MR spectroscopy. We found that chemogenetic induced nigro-striatal dopamine transmission lowers some of the stereotypic behaviors that are considered hallmarks of OCD. It also disrupts functional connectivity between cortical areas and striatum, and increased total glutamate and N-acetylaspatateglutamate in cortical regions. The results thus establishes the importance of nigro-striatal dopamine transmission in modulation of CSTC function and emphasize DMS dopamine as a possible target for treatment of related neuropsychiatric disorders.

show abstract

“…Current research on this topic is limited and ambiguous. Servaes et al showed that the [18F]-FDG uptake in the hippocampus decreased by 19.57% in rats chronically treated with QNP [36]. On the other hand, Carpenter et al reported that local cerebral glucose utilization in the hippocampus of QNP-treated rats remained unchanged when measured by the [14C]2-deoxyglucose [37].…”

Section: Discussionmentioning

confidence: 99%

Plasticity-Related Activity in the Hippocampus, Anterior Cingulate, Orbitofrontal, and Prefrontal Cortex Following a Repeated Treatment with D2/D3 Agonist Quinpirole

et al. 2021

View full text Add to dashboard Cite

Quinpirole (QNP) sensitization is a well-established model of stereotypical checking relevant to obsessive-compulsive disorder. Previously, we found that QNP-treated rats display deficits in hippocampus-dependent tasks. The present study explores the expression of immediate early genes (IEG) during QNP-induced stereotypical checking in the hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and medial prefrontal cortex (mPFC). Adult male rats were injected with QNP (0.5 mg/mL/kg; n = 15) or saline (n = 14) daily for 10 days and exposed to an arena enriched with two objects. Visits to the objects and the corners of the arena were recorded. QNP-treated rats developed an idiosyncratic pattern of visits that persisted across experimental days. On day 11, rats were exposed to the arena twice for 5 min and sacrificed. The expression of IEGs Arc and Homer1a was determined using cellular compartment analysis of temporal activity by fluorescence in situ hybridization. IEG-positive nuclei were counted in the CA1 area of the hippocampus, ACC, OFC, and mPFC. We found significantly fewer IEG-positive nuclei in the CA1 in QNP-treated rats compared to controls. The overlap between IEG expressing neurons was comparable between the groups. We did not observe significant differences in IEG expression between QNP treated and control rats in ACC, OFC, and mPFC. In conclusion, treatment of rats with quinpirole decreases plasticity-related activity in the hippocampus during stereotypical checking.

show abstract

[18F]-FDG PET neuroimaging in rats with quinpirole-induced checking behavior as a model for obsessive compulsive disorder

Cited by 11 publications

References 43 publications

Neuroreceptor kinetics in rats repeatedly exposed to quinpirole as a model for OCD

Neuroreceptor kinetics in rats repeatedly exposed to quinpirole as a model for OCD

Dorsal striatal dopamine induces fronto-cortical hypoactivity and implies reduced anxiety and compulsive behaviors in rats

Plasticity-Related Activity in the Hippocampus, Anterior Cingulate, Orbitofrontal, and Prefrontal Cortex Following a Repeated Treatment with D2/D3 Agonist Quinpirole

Contact Info

Product

Resources

About