Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex

Abstract

The quinpirole sensitization model of obsessive-compulsive disorder was used to investigate the functional role that brain regions implicated in a neuroanatomical circuit of obsessive-compulsive disorder may play in compulsive checking behavior. Following repeated injections of saline or quinpirole (0.5mg/kg, twice per week, ×8 injections) to induce compulsive checking, rats received N-methyl-d-aspartate lesions of the nucleus accumbens core (NAc), orbital frontal cortex (OFC) and basolateral amygdala, or sham lesions. When retested at 17days post-surgery, the results showed effects of NAc and OFC but not basolateral amygdala lesion. NAc lesions affected measures indicative of the amount of checking behavior, whereas OFC lesions affected indices of staying away from checking. The pattern of results suggested that the functional roles of the NAc and OFC in checking behavior are to control the vigor of motor performance and focus on goal-directed activity, respectively. Furthermore, similarities in behavior between quinpirole sham rats and saline NAc lesion rats suggested that quinpirole may drive the vigor of checking by inhibition of NAc neurons, and that the NAc may be a site for the negative feedback control of checking.

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

“…This measure is greatly reduced in quinpirole-sensitized rats and has been proposed to index the third constitutive component of compulsive checking behavior-"satiety" or rest after checking (Dvorkin et al 2010). It was reasoned (Dvorkin et al 2010) that, in the animal model, the foreshortened "satiety" or "rest" after a bout of checking corresponds to notions that OCD reflects failure to achieve "sense of task completion" (Pitman 1989) or "feeling of knowing" (Szechtman and Woody 2004).…”

“…It should be noted that a rat may complete a bout of checking but not start the next bout during the session, and hence, the number of rats for "time to next checking bout" is generally smaller than for the four criteria measures for compulsive checking. Saline-treated rats generally have one to two bouts of checking behavior in a session, while quinpirole-treated rats usually perform two or more bouts (Dvorkin et al 2010). …”

“…The criteria measures for compulsive checking were dissociated empirically in a recent lesion study (Dvorkin et al 2010). Specifically, nucleus accumbens core (NAc) lesions affected measures indicative of the amount of checking behavior (frequency of checking and length of check), whereas orbitofrontal cortex (OFC) lesions affected indices of staying away from checking the key locale (time to return to check and number of stops before returning to check).…”

“…Rats were tested on large open field (160×160 cm blue table without walls) located in a noncolony room, as described previously (Dvorkin et al 2006(Dvorkin et al , 2010. The table was divided virtually into a grid of 25 rectangular places (locales), but no actual lines were marked on the table surface.…”

Behavioral Tests for Evaluation of Information Processing and Cognitive Deficits in Rodent Animal Models of Neuropsychiatric Disorders

“…These may be straightforward hyperlocomotion in a pharmacological model of schizophrenia induced by NMDA receptor antagonists or compulsive adherence to specific routes and objects in animal models of obsessive-compulsive disorder (OCD induced by repeated systemic treatment with quinpirole, a D2-like receptor agonist. (Szechtman et al, 2001, Dvorkin et al, 2008Dvorkin et al, 2010;Woody and Szechtman, 2011). Nevertheless, they should not be anthropomorphized (such as a ´diseased rat´) but have the purpose to serve as model reproductions in laboratory animals of specific classes of symptoms of CNS disorders, rather than a disorder as a whole, despite common usage of the term of animal models in the latter .…”