Altered quinpirole-induced local cerebral glucose utilization in anterior cortical regions in rats after sensitization to quinpirole

Dopaminergic psychostimulants produce behavioral responses of greater magnitude with repeated, intermittent administration, than a single, acute dose, a phenomenon known as “sensitization.” Most studies of sensitization have focused on the “motive circuit”; however, some additional anterior cortical regions also appear to be affected. In this study, alterations in regional neuronal activity in anterior cortical brain areas produced by quinpirole, a D2/D3 agonist, 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 third day; controls and drug-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 11 anterior cortical brain regions by quantitative autoradiography. In drug-naive rats, quinpirole decreased LCGU in the cingulate cortex-area 3 (−16%) and infralimbic cortex (−16%). In sensitized rats, quinpirole decreased LCGU in the cingulate cortex-area 1 (−19%), frontal cortex-area 3 (−19%), lateral orbital cortex (−18%), medial/ventral orbital cortex (−17%), and parietal cortex (−17%) as well as in the cingulate cortex-area 3 (−19%) and infralimbic cortex (−20%); (all P < 0.05 v. control). This suggests that decreased neuronal activity in the cingulate cortex-area 1, frontal cortex-area 3, lateral orbital cortex, medial/ventral orbital cortex, and parietal cortex, in addition to altered activity in the motive circuit, may underlie the augmented behavioral response to quinpirole in sensitized animals.