Differences in quinpirole-induced local cerebral glucose utilization between naive and sensitized rats

Dopaminergic psychostimulants produce behavioral responses of greater magnitude with repeated, intermittent administration, than a single, acute dose, a phenomenon known as 'sensitization'. Alterations in regional neuronal activity produced by quinpirole, a D(2)/D(3) agonist, in quinpirole-naive and quinpirole-sensitized rats were assessed on the basis of local cerebral glucose utilization (LCGU) using the [14C]2-deoxyglucose (2-DG) method. Adult, male Long-Evans rats (180-200 g, n=7-9/group) were subjected to ten injections of quinpirole (0.5 mg/kg, s.c.) administered every 3rd day; controls and quinpirole-naive rats received saline. Locomotor activity was quantitated after injections one and ten to confirm sensitization. The 2-DG procedure was initiated 60 min after an 11th injection in freely moving rats. LCGU was determined in 43 brain regions by quantitative autoradiography. In quinpirole-naive rats, quinpirole decreased LCGU in the caudate/putamen (84% of control), lateral habenula (80% of control), and motor cortex (79% of control). In sensitized rats, quinpirole decreased LCGU in the nucleus accumbens core and shell (77 and 83% of control, respectively) and ventral pallidum (82% of control) as well as in the caudate/putamen (86% of control), lateral habenula (77% of control), and motor cortex (79% of control). This suggests that decreased neuronal activity in the nucleus accumbens and ventral pallidum may underlie the augmented behavioral response to quinpirole in sensitized animals.