Separate mechanisms for development and performance of compulsive checking in the quinpirole sensitization rat model of obsessive-compulsive disorder (OCD)

Abstract

Findings show that mCPP inhibits performance of compulsive checking but does not block quinpirole from inducing the neural substrate underlying this compulsive behavior. Hence, a separate mechanism underlies the induction of compulsive checking and the performance of it. It is suggested that development of the OCD endophenotype reflects neuroplastic changes produced by repeated dopamine D2/D3 receptor stimulation, while stimulation of serotonergic receptors mediates a negative feedback signal that shuts down the motor performance of checking.

Obsessive-compulsive disorder: Insights from animal models

“…Moreover, the rats seemed to travel hurriedly from place to place with unbounded curiosity as if performing an important mission, and they did not appear to habituate to the environment or succumb to fatigue (Szechtman et al, 1994b). This behavior of QNP rats was suggested as a model for compulsive checking (Szechtman et al, 1998a) and was further supported in a large set of studies (e.g., Alkhatib et al, 2013; Tucci et al, 2013, 2014b). This compulsive-like behavior of QNP rats in the open field is based on two types of performance: (i) path stereotypy; and (ii) fixed sets of acts in specific locations (see Section 5 and Fig.…”

“…Such concordance between predictive and construct validity is especially significant. 5HT 1A agonists reduce stereotypy (Korff et al, 2008; Tucci et al, 2013, 2014b), while 5-HT 1A receptor activation promotes adenylyl cyclase sensitization (Hensler et al, 1996), supporting a role for 5HT 1A/B G i dependent adenylate cyclase-cAMP coupling in OCD (Marazziti et al, 2001; Perez et al, 2001) and its response to treatment. Indeed, clinically effective OCD treatments prevent 5-HT 1B receptor-induced repetitive behavior and striatal activation (Ho et al, 2015).…”

From an animal model to human patients: An example of a translational study on obsessive compulsive disorder (OCD)

“…Alkhatib et al, 2013;Tucci et al, 2013Tucci et al, , 2014, it was also criticized (Alonso et al, 2015), suggesting that the rats' behavior could be considered as drug stereotypy, (de Haas et al, 2011(de Haas et al, , 2012. Indeed, after administering other psychoactive drugs, such as amphetamine, traveling along the same path and performing the same acts in the same places also prevailed Golani, 1990, 1994).…”

Nucleus accumbens core and pathogenesis of compulsive checking

“…Consistent with the above clinical findings are results from animal studies where DBS of the nucleus accumbens and related sites was effective in attenuating compulsive checking (Winter et al , 2008; Mundt et al , 2009; Djodari-Irani et al , 2011; Winter, 2012) in the same quinpirole sensitization rat model of compulsive checking as used in the present study. Finally, a contribution of the nucleus accumbens may be expected, given that a lesion of the NAc produces hyperactivity (Cardinal et al , 2001; Dvorkin et al , 2010; Tucci et al , 2014b), raising the possibility that such hyperactive rats may develop compulsive checking faster with repeated injections of quinpirole.…”