Basal local cerebral glucose utilization is not altered after behavioral sensitization to quinpirole

Abstract

Sensitization to psychostimulants results in a behavioral response of a greater magnitude than that produced by a given single dose. Previously, we have shown that sensitization to the D 2 /D 3 dopamine receptor agonist quinpirole produces alterations in quinpirole-stimulated local cerebral glucose utilization (LCGU) in ventral striatal and limbic cortical regions. To determine whether basal neuronal activity is altered in the sensitized animal, this study examined the effects of a sensitizing course of quinpirole on basal neuronal activity using the [ 14 C]-2-deoxyglucose (2-DG) method in rats with verified sensitization. Adult, male Long-Evans rats (n = 7 or 10/group) were subjected to 10 injections of quinpirole (0.5 mg/kg, s.c.) or saline administered every 3 rd day. Sensitization was verified on the basis of locomotor activity. The 2-DG procedure was performed in freely moving rats three days after the last quinpirole injection. LCGU was determined by quantitative autoradiography. No alterations in basal LCGU were detected in quinpirole-sensitized rats compared to those treated with saline. The present finding suggests that either the basal activity of very discrete populations of neurons is affected by sensitization to quinpirole or that the neurobiological changes that result in the sensitized behavioral response affect only stimulated, but not basal, neuronal activity.

Features of compulsive checking behavior mediated by nucleus accumbens and orbital frontal cortex

“…The fact that a cell-body lesion yielded quinpirole-like effects argues furthermore for an inhibitory action of quinpirole on NAc neurons, releasing their inhibitory control over other neural sites to increase checking intensity. Such a quinpirole inhibitory mechanism is consistent with several lines of evidence: electrophysiological findings that NAc applications of quinpirole inhibit neuronal firing of accumbal medium spiny neurons (Perez et al, 2006); findings from 2-deoxyglucose autoradiography that a specific effect of chronic treatment with quinpirole (compared with acute quinpirole) is a reduction of glucose metabolism in the nucleus accumbens (Carpenter et al, 2003;Richards et al, 2007); the suggestion from mice over-expressing striatal D2 receptors that the basal metabolic rate for glucose is reduced there (Kellendonk et al, 2006); and, finally, the results of the present study showing that NAc lesions elevate checking under saline, without doing so under quinpirole.…”

“…, 2006); findings from 2‐deoxyglucose autoradiography that a specific effect of chronic treatment with quinpirole (compared with acute quinpirole) is a reduction of glucose metabolism in the nucleus accumbens (Carpenter et al. , 2003; Richards et al. , 2007); the suggestion from mice over‐expressing striatal D2 receptors that the basal metabolic rate for glucose is reduced there (Kellendonk et al.…”