Modulation of quinpirole-induced compulsive-like behavior in rats by environmental changes: Implications for OCD rituals and for exploration and navigation

Abstract

Background: Rats treated chronically with the D 2-3 dopamine agonist quinpirole were previously proposed as an animal model of obsessive-compulsive disorder (OCD) since their behavior is based on repeated, compulsive-like persistent traveling between a few places in the open field. The aim of the present study was to determine properties of the physical environment that shape such behavior. For this, quinpirole-treated rats were first exposed to an arena with an array of objects (landmarks) and after the development of compulsive-like behavior, the arena was manipulated by multiplying the number of objects, changing their spacing, relocating object array, or removing the objects.

Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model of Compulsive Checking

“…All injections were administered subcutaneously at a volume of 1 ml/kg. The dose administered (0.5 mg/kg) was consistent with previous research on the behavioral effects of quinpirole (see Amato et al, 2007;Milella et al, 2008;Zadicario et al, 2007).…”

“…Perhaps the drug caused the animals to more evenly distribute their time among the stimuli in the chamber. However, it should be noted that in open-field tests, rats treated chronically with quinpirole have been observed to preferentially visit one or a few locations more frequently than others (Zadicario et al, 2007). Thus, while the sampling may not always occur evenly across the environment, quinpirole-treated animals show a propensity toward more frequent checking of environmental features and are not simply preoccupied with a single feature.…”

“…A persistent preoccupation with one location in the environment is another commonly observed effect (Alkhatib, Dvorkin-Gheva, & Szechtman, 2013). However, the behavior of quinpiroletreated rats is not entirely fixed as it often changes when the environment is altered (Szechtman et al, 2001;Zadicario, Ronen, & Eilam, 2007). Thus, as with compulsions in patients with OCD, the behavior of quinpirole-treated rats has been characterized as "flexible, yet recurrent" (Szechtman et al, 1998).…”

Repeated intranigral MPTP administration: A new protocol of prolonged locomotor impairment mimicking Parkinson's disease

“…Additionally, we performed the same procedure 1 and 3 days after the 2nd and the 3rd MPTP administrations. This method of motor activity evaluation has been validated in several reports that have referred to the use of dopaminergic agonists and antagonists (Del Arco et al, 2007;Perry et al, 2004;Queiroz et al, 2002;Zadicario et al, 2007). Locomotor assessment began by placing the rats in the same position of the open-field.…”

Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive–compulsive disorder (OCD)

“…Third, quinpirole-induced compulsive checking is subject to similar modulation as OCD compulsions in that the performance of each is modified by external stimuli and can be suppressed temporarily (Ben Pazi et al 2001;Szechtman et al 2001;Zadicario et al 2007). Finally, treatments that are therapeutically useful for OCD are also effective in attenuating quinpirole-induced compulsive checking, e.g., clomipramine (Foa et al 2005;Szechtman et al 1998), nicotine (Lundberg et al 2004;Salin-Pascual and Basanez-Villa 2003;Tizabi et al 2002), and deep brain stimulation (Djodari-Irani et al 2011;Greenberg et al 2006;Mundt et al 2009;Winter et al 2008).…”