Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessiveâ[euro]"compulsive disorder (OCD)

The serotonergic agonist, meta-chlorophenylpiperazine (mCPP), produces inconsistent effects on obsessiveâ[euro]"compulsive disorder (OCD) symptoms, perhaps because clinical studies have not utilized a homogenous OCD subgroup of patients. This study aimed to evaluate mCPP effects on functional components of compulsive checking, using the quinpirole sensitization rat model of OCD. In study 1, the effects of mCPP were evaluated in quinpirole rats with compulsive checking. Two experimental groups were co-injected with quinpirole (0.125Â mg/kg) and mCPP (0.625 or 1.25Â mg/kg), while one control group was co-injected with quinpirole (0.125Â mg/kg) and saline and the other control group received co-injections of saline. In study 2, mCPP (0, 0.3125, 0.625, and 1.25Â mg/kg) was administered repeatedly to naive rats and induction of compulsive checking evaluated. 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 naive rats, mCPP did not induce compulsive behavior, but the highest dose reduced vigor of checking performance compared to saline controls. 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 5HT^sub 2A/2C^ receptors in substantia nigra pars reticulata that inhibit expression of motor vigor.[PUBLICATION ABSTRACT]