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.

• Keywords
• Arc, Homer1, hippocampus, obsessive-compulsive disorder, quinpirole, stereotypical checking,
• MeSH
• Dopamine D2 Receptor Antagonists pharmacology   MeSH
• Quinpirole pharmacology   MeSH
• Gyrus Cinguli drug effects   physiology   MeSH
• Hippocampus drug effects   physiology   MeSH
• Rats MeSH
• Neurons drug effects   metabolism   MeSH
• Neuronal Plasticity drug effects   physiology   MeSH
• Genes, Immediate-Early MeSH
• Motor Activity drug effects   MeSH
• Rats, Long-Evans MeSH
• Prefrontal Cortex drug effects   physiology   MeSH
• Receptors, Dopamine D2 metabolism   MeSH
• Receptors, Dopamine D3 antagonists & inhibitors   MeSH
• Gene Expression Regulation drug effects   MeSH
• Stereotyped Behavior drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Dopamine D2 Receptor Antagonists MeSH
• Quinpirole MeSH
• Receptors, Dopamine D2 MeSH
• Receptors, Dopamine D3 MeSH

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with 1-3% prevalence. OCD is characterized by recurrent thoughts (obsessions) and repetitive behaviors (compulsions). The pathophysiology of OCD remains unclear, stressing the importance of pre-clinical studies. The aim of this article is to critically review a proposed animal model of OCD that is characterized by the induction of compulsive checking and behavioral sensitization to the D2/D3 dopamine agonist quinpirole. Changes in this model have been reported at the level of brain structures, neurotransmitter systems and other neurophysiological aspects. In this review, we consider these alterations in relation to the clinical manifestations in OCD, with the aim to discuss and evaluate axes of validity of this model. Our analysis shows that some axes of validity of quinpirole sensitization model (QSM) are strongly supported by clinical findings, such as behavioral phenomenology or roles of brain structures. Evidence on predictive validity is contradictory and ambiguous. It is concluded that this model is useful in the context of searching for the underlying pathophysiological basis of the disorder because of the relatively strong biological similarities with OCD.

• Keywords
• OCD, animal model, brain circuits, human, quinpirole, rat,
• Publication type
• Journal Article MeSH
• Review MeSH