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


OBJECTIVE
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.
Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.
Mark C
MC
Tucci
Anna
A
Dvorkin-Gheva
Dawn
D
Graham
Sean
S
Amodeo
Paul
P
Cheon
Ashley
A
Kirk
John
J
Peel
Leena
L
Taji
Henry
H
Szechtman
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003192:Compulsive Behavior / Q000139:chemically induced; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D019257:Quinpirole / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D010879:Piperazines; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; C015068:1-(3-chlorophenyl)piperazine