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 D(2)/D(3) agonist, were assessed on the basis of local cerebral glucose utilization (LCGU) using the [(14)C]-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.
Richards
Toni L
TL
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA.
Pazdernik
Thomas L
TL
Levant
Beth
B
D000818:Animals; D001345:Autoradiography; D002250:Carbon Radioisotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D019257:Quinpirole / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans
D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D019257:Quinpirole; D003847:Deoxyglucose; D005947:Glucose