Clorgyline-induced modification of behavioral sensitization to quinpirole: effects on local cerebral glucose...

Sensitization refers to augmented behavioral responses produced by repeated, intermittent injections of dopaminergic psychostimulants. The locomotor manifestations observed after a sensitizing course of quinpirole, a D(2)/D(3) dopamine agonist, can be modified by the MAO(A) inhibitor clorgyline, by a mechanism apparently unrelated to its actions on MAO(A). Alterations in regional neuronal activity produced by quinpirole in quinpirole-sensitized rats with or without clorgyline pretreatment were assessed based on LCGU using the [(14)C]-2-deoxyglucose (2-DG) method. Adult, male Long-Evans rats (180-200 g, n=9-10/group) were subjected to an injection of either clorgyline (1.0 mg/kg, s.c.) or saline 90 min prior to an injection of quinpirole (0.5 mg/kg, s.c.) or saline, 1 set of injections administered every 3rd day for 10 sets. The 2-DG procedure was initiated 60 min after an 11th set of injections in freely moving rats. LCGU was determined by quantitative autoradiography. LCGU was decreased in a number of limbic (nucleus accumbens and ventral pallidum) and cortical (medial/ventral orbital and infralimbic) regions and in the raphe magnus nucleus in quinpirole-sensitized rats (P<0.05 vs. saline-saline). Quinpirole-sensitized rats pretreated with clorgyline had similar alterations in LCGU, but LCGU was higher in the locus coeruleus compared to quinpirole alone (P<0.05), was not decreased in the raphe magnus nucleus, and was decreased in the piriform cortex and septum. This implicates altered activity of the noradrenergic, serotonergic, olfactory, and limbic systems in the modified behavioral response to quinpirole with clorgyline pretreatment.