Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive–compulsive disorder

Abstract

These results establish the sensitivity of the rewarded alternation OCD model to D2, 3 receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

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

“…In particular, Korff et al (2008) reported that mCPP attenuated the spontaneous high levels of compulsive-like behavior in deer mice. Similarly, in the reinforced spatial alternation model of OCD, mCPP attenuated the expression of compulsivelike behavior in rats (Kontis et al 2008;Tsaltas et al 2005). Conceivably, reduction of compulsive-like behavior in these animal models also involves an attenuation of the vigor with which those behaviors are performed.…”

“…1-(3-Chlorophenyl)-piperazine hydrochloride (mCPP) was administered to rats at doses of 0.625 or 1.25 mg/kg. These doses of mCPP were chosen because they produce compulsive-like behavior in a rat model (Kontis et al 2008). (−)-Quinpirole hydrochloride was administered at a dose of 0.125 mg/kg (rather than 0.5 mg/kg; Dvorkin et al 2006;Szechtman et al 1998) to minimize the possibility that a full dose of quinpirole produces a ceiling effect on compulsive checking that would mask a potential exacerbation with mCPP cotreatment.…”

“…Using deer mice, (Korff et al 2008) found that mCPP reduced compulsive behaviors. However, in another model-the reinforced spatial alternation model of OCD (Kontis et al 2008;Tsaltas et al 2005), the effects of mCPP were biphasic: early mCPP treatment exacerbated the model compulsive behavior, while chronic treatment with mCPP attenuated it.…”

Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior

“…We hypothesized that quinpirole, which has been consistently implicated in compulsive behavior (Szechtman et al , 2001Joel et al 2001;Kontis et al 2008), would specifically impair response inhibition and that drug effects would be apparent during reversal but not retention of the original discrimination. Further, we aimed to investigate the distinct involvement of D2 and D3 receptor subtypes in spatial reversal learning by (a) testing the effects of systemic administration of the D2/D3 receptor antagonist raclopride (selective D2 receptor agonists and antagonists not being available) and determining whether it abolishes the quinpirole-induced reversal impairment following combined administration and (b) determining the effects of systemic administration of the selective D3 receptor antagonist nafadotride in combination with quinpirole.…”

Dissecting OCD Circuits: From Animal Models to Targeted Treatments

“…These include barbering (repetitive hair biting and pulling), acral paw-lick (repetitive canine paw-licking), zoorelated stereotypies, and marble burying. In addition to these models of spontaneouslygenerated behaviors, many groups have studied induced repetitive behaviors including: 1) perseverative lever-pressing in the absence of reward 83 ; 2) persistent revisiting of unrewarded arms in a T-maze 84 ; and 3) pharmacologically-induced compulsive checking 85 and perseverative locomotion 38 . All of these models can be used to dissect circuits underlying stereotyped behaviors via either targeted lesions or drug injections through stereotactically-placed cannulae.…”