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Updated: May 14, 2026
Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder
Published on: January 9, 2015
Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive-compulsive
Mark C Tucci1, Anna Dvorkin-Gheva, Dawn Graham
1Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Rationale:
The serotonergic agonist, meta-chlorophenylpiperazine (mCPP), produces inconsistent effects on obsessive-compulsive disorder (OCD) symptoms, perhaps because clinical studies have not utilized a homogenous OCD subgroup of patients.
Objectives:
This study aimed to evaluate mCPP effects on functional components of compulsive checking, using the quinpirole sensitization rat model of OCD.
Methods:
In study 1, the effects of mCPP were evaluated in quinpirole rats with compulsive checking. Two experimental groups were co-injected with quinpirole (0.125 mg/kg) and mCPP (0.625 or 1.25 mg/kg), while one control group was co-injected with quinpirole (0.125 mg/kg) and saline and the other control group received co-injections of saline. In study 2, mCPP (0, 0.3125, 0.625, and 1.25 mg/kg) was administered repeatedly to naïve rats and induction of compulsive checking evaluated.
Results:
mCPP significantly attenuated quinpirole-induced compulsive checking behavior by reducing vigor of checking (indexed by frequency of checking and length of check) and increasing rest after a bout of checking (indexed by time to the next checking bout), but it did not affect focus on the task of checking (indexed by recurrence time of checking and number of stops before returning to check). In naïve rats, mCPP did not induce compulsive behavior, but the highest dose reduced vigor of checking performance compared to saline controls.
Conclusions:
mCPP did not exacerbate or induce compulsive checking behavior. Instead, it ameliorated compulsive checking by reducing vigor of checking and increasing post-checking satiety, without affecting focus on checking. Ameliorative effects of mCPP may involve 5HT2A/2C receptors in substantia nigra pars reticulata that inhibit expression of motor vigor.
Insights
Meta-chlorophenylpiperazine (mCPP) did not worsen or cause compulsive checking in rats. Instead, it reduced the vigor of checking behaviors and increased rest periods, suggesting potential therapeutic benefits for obsessive-compulsive disorder (OCD).
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Inconsistent effects of meta-chlorophenylpiperazine (mCPP) on obsessive-compulsive disorder (OCD) symptoms may stem from patient heterogeneity.
- The quinpirole sensitization rat model offers a homogenous platform to study OCD-related behaviors.
Purpose of the Study:
- To investigate the effects of mCPP on functional components of compulsive checking behavior.
- To utilize the quinpirole sensitization rat model to assess mCPP's impact on OCD-like behaviors.
Main Methods:
- Study 1: Evaluated mCPP (0.625 or 1.25 mg/kg) co-injected with quinpirole (0.125 mg/kg) in rats exhibiting compulsive checking.
- Study 2: Administered repeated doses of mCPP (0-1.25 mg/kg) to naive rats to assess induction of compulsive checking.
Main Results:
- mCPP significantly reduced quinpirole-induced compulsive checking by decreasing checking vigor and increasing post-checking rest.
- mCPP did not influence the focus of checking behavior (e.g., recurrence time, stops).
- In naive rats, mCPP did not induce compulsive behavior; higher doses reduced checking vigor.
Conclusions:
- mCPP ameliorates, rather than exacerbates or induces, compulsive checking behavior.
- The observed ameliorative effects are linked to reduced checking vigor and increased post-checking satiety.
- Potential mechanisms involve 5-HT2A/2C receptors in the substantia nigra pars reticulata influencing motor vigor.
