Baseline plasma glucose concentrations prior to the initiation of the 2DG procedure were not different between drug-naïve controls and cocaine-experienced animals (controls, 144.2 ± 6.7 mg/mL; 48 h withdrawal from cocaine, 153.4 ± 17.0 mg/mL). Selumetinib mouse Rates of local cerebral glucose metabolism were measured in 20 brain regions and the data are shown in Table 1. These rates were globally lower in animals with a history

of cocaine self-administration measured 48 h after the final self-administration session as compared with drug-naïve controls (84.5 ± 4.7 vs. 74.6 ± 4.4 μmol/100 g/min cocaine-withdrawal, t11 = 2.245, P < 0.05). This pattern was observed in all 20 of the regions in which glucose utilization rates were measured. In the cortex, two-way anova revealed a main effect of treatment (F1,11 = 5.95, P < 0.05) and brain region (F2,22 = 151.9, P < 0.001), but no interaction. In the basal ganglia, there was a main effect of treatment (F1,11 = 8.10 P < 0.05) and brain region (F5,55 = 125.67, P < 0.001), but no interaction. In limbic brain areas, there was a main effect of treatment (F1,11 = 6.10 P < 0.05) and brain region (F7,77 = 110.3, P < 0.001), and an interaction (F7,70 = 3.041, P < 0.05).

Finally, in the brainstem, there was PD0325901 mw a main effect of treatment (F1,11 = 12.48, P < 0.01) and brain region (F2,22 = 75.21, P < 0.001), but no interaction. Planned multiple comparisons showed that 48 h after cocaine self-administration functional activity was lower in the anterior cingulate cortex (−12%), dorsal caudate putamen (−16%), nucleus accumbens (-16%, Fig. 5), basolateral amygdala

(−16%), medial nucleus of the thalamus (−12%), hippocampal CA1 region (−24%, Fig. 5), dorsal raphe (−18%), locus coeruleus (−13%) and cerebellum (−15%), when compared with controls. Here we demonstrate that there are functional and behavioral reductions present 48 h after 5-day cocaine self-administration. The functional alterations were characterized by reduced brain activity, as indicated by lower rates Methane monooxygenase of cerebral glucose utilization, in circuits involved in learning and memory, attention, sleep, and reward processing. These data are consistent with human studies that have demonstrated marked reductions in functional brain activity, in particular prefrontal cortical and striatal regions, which occur early in the withdrawal period and last for up to 4 months following cocaine misuse (Volkow et al., 1992, 1993). Previously, we have shown that cocaine self-administration resulted in reductions in functional activity, but these effects were measured immediately following the final infusion at a time when cocaine levels were still high (Macey et al., 2004).