Behavioral pattern analysis and dopamine release in quinpirole-induced repetitive behavior in rats

Abstract

Obsessive-compulsive disorder (OCD) is a chronic and disabling psychiatric disease with a lifetime prevalence of 2-3%. People with OCD suffer from intrusive, unwanted and recurrent thoughts (obsessions) and/or repetitive ritualistic behaviors (compulsions). The aim of this study is to quantify the dimensions of ritualistic 'compulsive-like' behavior in quinpirole-induced behavior in rats by using T-pattern behavioral analysis. In addition, we investigated whether the behavioral effects elicited by quinpirole sensitization remained after 2 weeks of cessation of treatment. Finally, to study the neurobiological underpinnings of this 'compulsive-like' behavior, we investigated the effect of quinpirole treatment on the extracellular dopamine levels in the nucleus accumbens. Once established, 'compulsive-like' behavior is dependent upon quinpirole administration, as this behavior rapidly normalized after cessation of treatment. After a single dose of quinpirole the dopamine level decreased more in saline pre-treated animals as compared with animals given quinpirole treatment continuously. Furthermore, T-pattern analysis revealed that quinpirole-induced behavior consists, unlike OCD rituals, of a smaller behavioral repertoire. As seen in patients with OCD, quinpirole-treated animals performed these behaviors with a high rate of repetition. These findings suggest that quinpirole-induced behavior mimics only part of the compulsive behavior as shown in OCD patients.

Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function

“…First, the initial hypoactivity observed in response to quinpirole administration is due to activation of release-regulating presynaptic D2 receptors (i.e. autoreceptors), which leads to decreased dopamine release in the NAc (de Haas et al 2011). Indeed, there is evidence that following repeated quinpirole administration these D2 autoreceptors become subsensitive, attenuating the effects of quinpirole on dopamine release and thereby eliminating this initial phase of hypoactivity (de Haas et al 2011).…”

“…autoreceptors), which leads to decreased dopamine release in the NAc (de Haas et al 2011). Indeed, there is evidence that following repeated quinpirole administration these D2 autoreceptors become subsensitive, attenuating the effects of quinpirole on dopamine release and thereby eliminating this initial phase of hypoactivity (de Haas et al 2011). In contrast, the subsequent locomotor activating effects observed in response to acute quinpirole are due to direct activation of postsynaptic D2 receptors in the NAc (Dreher and Jackson 1989; Phillips et al 1995; Wu et al 1993).…”

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

“…Increases in the motor activity of rats as a result of Mn exposure have been reported previously (Calabresi et al, 2001; Kern et al, 2010), though these effects are often transient (Vacher et al, 2006). Repetitive turning was also observed in Mn-exposed rats, which may contribute to the overall increased activity, but has also been associated with stereotypy linked to dopaminergic dysfunction, akin to obsessive compulsive disorders (de Haas et al, 2010). While repetitive turning was significantly elevated in Mn-exposed rats the distribution of repetitive turning events was consistent with the circadian behavior of control animals, unlike rearing, sniffing and grooming (Figure 5C).…”

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

“…Importantly these changes were not seen after acute treatment with quinpirole (Carpenter et al, 2003). Additionally, de Haas et al (2011) have shown alterations in dopamine efflux in the nucleus accumbens in the QSM compared to intact animals.…”