Potential involvement of the locus coeruleus in the behavioral manifestations of obsessive-compulsive disorder: evidence from the quinpirole sensitization model

Abstract

Quinpirole sensitization is used as an animal model of obsessive-compulsive disorder (OCD), a psychiatric disorder characterized by excessive, repetition of an obsession and/or compulsion. Clorgyline, an MAOA inhibitor, modifies the quinpirole-sensitized behavioral response by a mechanism apparently unrelated to its activity at MAOA. Thus, clorgyline pretreatment extends this animal model by simulating variations seen in human OCD symptomology. Alterations in regional neuronal activity produced by quinpirole in quinpirole-sensitized rats with or without clorgyline pretreatment were assessed on the basis of LCGU using the [14C]-2-deoxyglucose (2-DG) method. Adult, male Long-Evans rats (180-200 g, n = 9-10/group) were injected with clorgyline (1 mg/kg, s.c.) or saline 90-minutes prior to an injection of quinpirole (0.5 mg/kg, s.c.) or saline, 1 set of injections given every third day. The 2-DG procedure was initiated 60-minutes after an eleventh set of injections in freely moving rats. LCGU was determined by quantitative autoradiography. In quinpirole-sensitized rats, LCGU was decreased in a number of limbic, cortical, and motor regions and in the raphe magnus nucleus (P<0.05 v. controls). Quinpirole-sensitized rats pretreated with clorgyline had similar alterations in LCGU, but LCGU was also decreased in the piriform cortex and septal area (P<0.05 v. controls), was not decreased in the raphe magnus nucleus, and was increased in the locus coeruleus compared to quinpirole alone (P<0.05). This implicates altered activity of the limbic, serotonergic, and especially the noradrenergic systems in the modified behavioral response to quinpirole with clorgyline pretreatment and speculatively in the variations seen in human OCD symptomology.