Quinpirole induces compulsive checking behavior in rats: A potential animal model of obsessive-compulsive disorder (OCD).

Abstract

Rats treated chronically with the dopamine agonist quinpirole (0.5 mg/kg, twice weekly X 10) met 5 criteria for performance of compulsive checking. Specifically, in a large open-field with single small objects in 4 of 25 locales, quinpirole rats revisited two places/objects excessively often and rapidly, compared with other locations in the environment or saline controls. They performed a ritual-like set of behavioral acts at these two places/objects and stopped in relatively few locales before returning to the preferred places/objects. Finally, they shifted their behavior to a new location when the object was moved there. Clomipramine (10 mg/kg, daily) postponed but did not prevent the development of the quinpirole effect. Quinpiroleinduced compulsive checking may be an exaggeration of normal checking of home site in rats.Results suggest an animal model of obsessive-compulsive disorder and a role for dopamine in this disorder.

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

“…Behavioral sensitization is of much interest because of its potential relevance to several human pathologies ranging from drug addiction to schizophrenia (Kalivas and Stewart, 1991;Koob and Le Moal, 1997;Robinson and Becker, 1986;Segal and Schuckit, 1983) and obsessive-compulsive disorder (Eilam and Szechtman, 2005;Szechtman et al, 1998Szechtman et al, , 2001Tizabi et al, 2002). Responses that sensitize with chronic drug treatment may include locomotion, sniffing, licking, or biting.…”

Obsessive-Compulsive Disorder as a Disturbance of Security Motivation.

“…Our conception of OCD implies that under some circumstances, nonhuman animals should show OCD-like, maladaptively repetitive behavior, and this indeed has been an active area of research (e.g., Dodman, MoonFenelli, Mertens, Pfueger, & Stein, 1997;Pitman, 1989). For example, Szechtman, Sulis, and Eilam (1998) have investigated a drug-induced model of OCD, in which chronic treatment of rats with the dopamine agonist quinpirole induces compulsive checking behavior that is partly attenuated by clomipramine. The presently proposed theory of OCD indicates specifically where to look to explain compulsive behavior-namely, dysfunction in a satiety mechanism that connects the performance of security-related behaviors as inhibitory feedback to a subsystem that generates and sustains security motivation.…”

Selective Alleviation of Compulsive Lever-Pressing in Rats by D1, but not D2, Blockade: Possible Implications for the Involvement of D1 Receptors in Obsessive–Compulsive Disorder

“…Thus, Szechtman and colleagues have found that repeated administration of the D 2 agonist quinpirole induces compulsive checking behavior in rats (Eilam and Szechtman, 1995;Szechtman et al, 1998). Campbell et al (1999a-c) created a transgenic mouse model of OCD in which the function of D 1 receptor-expressing neurons in cortical and limbic regions is selectively potentiated, leading to a variety of compulsive-like behaviors, including episodes of perseverance of normal behaviors, repetitive leaping and repetitive nonaggressive biting of siblings.…”