Small animal PET provides insights into the effects of an acute opiate challenge on brain metabolism and behavior in adolescent versus adult animals

Objectives Using 18FDG, we examined metabolic ‘signatures’ that represent brain regions correlated with behaviors in adolescent versus adult animals.

Methods Adolescent (PND 30) and adult (PND 90) male Sprague-Dawley rats received an acute injection of morphine (10 mg/kg i.p.) during 18FDG uptake. Animals were scanned for 10 mins.

Results An acute dose of morphine produced significant behavioral alterations. Imaging data showed that, compared to the awake resting baseline scans, the magnitude of response in specific regions of the adolescent brain were much higher than those observed in adults. Compared to adults, adolescents had relatively larger increases in the amygdala, insular cortex, ventral hippocampus and hypothalamus. More significant decreases in metabolic demand occurred in the dorsal striatum and thalamus of adolescent animals. In adult animals, acute morphine changed metabolic activity in the same regions only to a lesser extent, although adult animals were distinguished by their response in the frontal and parietal cortices and dorsal hippocampus. Both age groups showed significant behavioral differences from the resting baseline state, with adolescent animals showing a more significant intoxication (p<0.001) than adults (p<0.05). Using 18FDG-PET imaging, we were able to determine a morphine-induced network of metabolic changes pertinent to both adolescent and adult populations. The more robust metabolic response observed in adolescents is consistent with clinical observations of increased abuse liability to opiates in adolescents versus teens.

Conclusions The more robust metabolic response observed in adolescents is consistent with clinical observations of an increased abuse liability to opiates in adolescents versus adult animals. Finally these data suggest that treatment strategies may also have to differ across ages.

Research Support This research was supported by the NIH and the DoD (K02-DA22346 to SLD; RC1-E4018534, PR094020 and DA25729 to WKS)