Spatial Reversal Learning in Chronically Sensitized Rats and in Undrugged Sensitized Rats with Dopamine D2-Like Receptor Agonist Quinpirole

Abstract

Dopamine plays a role in generating flexible adaptive responses in changing environments. Chronic administration of D2-like agonist quinpirole (QNP) induces behavioral sensitization and stereotypical behaviors reminiscent of obsessive–compulsive disorder (OCD). Some of these symptoms persist even after QNP discontinuation. In QNP-sensitization, perseverative behavior has often been implicated. To test the effect of QNP-sensitization on reversal learning and its association with perseveration we selected an aversively motivated hippocampus-dependent task, active place avoidance on a Carousel. Performance was measured as the number of entrances into a to-be-avoided sector (errors). We tested separately QNP-sensitized rats in QNP-drugged and QNP-undrugged state in acquisition and reversal tasks on the Carousel. In acquisition learning there were no significant differences between groups and their respective controls. In reversal, QNP-sensitized drugged rats showed a robust but transient increase in number of errors compared to controls. QNP-sensitized rats in an undrugged state were not overtly different from the control animals but displayed an altered learning manifested by more errors at the beginning compensated by quicker learning in the second session compared to control animals. Importantly, performance was not associated with perseveration in neither QNP-sensitized drugged nor QNP-sensitized undrugged animals. The present results show that chronic QNP treatment induces robust reversal learning deficit only when the substance is continuously administered, and suggest that QNP animal model of OCD is also feasible model of cognitive alterations in this disorder.

Rodent models of obsessive compulsive disorder: Evaluating validity to interpret emerging neurobiology

“…In contrast, other models lead to a novel stereotyped, repetitive pattern of behavior, as is seen with dopaminergic (quinpirole) and serotonergic (8-OHDPAT) agonists that induce perseverative locomotor behavior in the Y-maze or open field chambers (Yadin et al, 1991, Szechtman et al, 1998). Other measures, such as reversal learning or prepulse inhibition deficits, parallel findings that are not explicitly diagnostic but are instead thought to underlie the symptoms of OCD, such as cognitive rigidity or motor inhibition deficits (Chamberlain et al, 2006, Remijnse et al, 2006, Gu et al, 2008, Valerius et al, 2008, Andersen et al, 2010, Ahmari et al, 2012, Bissonette and Powell, 2012, Brigman et al, 2012, Remijnse et al, 2013, Hatalova et al, 2014, Zhang et al, 2015). …”

Validity of Quinpirole Sensitization Rat Model of OCD: Linking Evidence from Animal and Clinical Studies

“…As mentioned above, SA was found deficient in the QSM (Einat and Szechtman, 1995). Moreover, a significant deficit in the QSM was found in reversal learning (Boulougouris et al, 2009; Hatalova et al, 2014). Beside implications for OCD, these findings also suggest the involvement of D2/D3 receptors in these types of flexible behavior.…”

Higher Doses of (+)MK-801 (Dizocilpine) Induced Mortality and Procedural but Not Cognitive Deficits in Delayed Testing in the Active Place Avoidance With Reversal on the Carousel

“…To further investigate the consequences of psychotic episodes on late place memory, cognitive coordination and flexibility (Hatalova et al 2014) and spatial representation, we have designed a study in which (+)MK-801 was applied at doses 3 mg/kg and 5 mg/kg in a single injection and delayed testing in active place https: //doi.org/10.33549/physiolres.932832 Vol. 64 avoidance with reversal on a Carousel (commencing 10 days after application) demanding cognitive coordination and flexibility (Wesierska et al 2005).…”