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

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.