Metabolic and behavioral responses to acute and chronic morphine

Objectives Rodents administered sub-chronic escalating doses of morphine exhibit decreases in relative glucose metabolism in the frontal cortex, thalamus, and cerebellum. These region-specific changes are consistent with human behaviors associated with drug use and addiction. The role of regional differences in brain metabolism between acute and chronic drug use to disease progression and treatment has not been fully considered, if at all. Using 18FDG and Micro Positron Emission Tomography (MicroPET), we show that morphine administered acutely in rodents has an opposite effect on brain metabolism compared to rodents undergoing chronic morphine exposure.

Methods Two groups of adult male rats received serial FDG PET scan. Group 1 received a single dose of morphine (10mg/kg) 15min prior to FDG. Group 2 was treated with escalating doses of morphine for 14 days (10mg/kg to 42.5mg/kg). FDG scans occurred baseline and after 1, 7, and 21 days of withdrawal. Behavioral measures were obtained during and after morphine treatment.

Results Acutely, morphine significantly increased FDG uptake in the striatum and decreased uptake in the frontal cortex and cerebellum (see Figure). Sub-chronic treatment resulted in persistent decreases in FDG uptake in both cortical (frontal, parietal, temporal cortices) and subcortical structures (deep cerebellar nuclei, striatum, thalamus). Behavioral measures of withdrawal severity correlated with regional changes in FDG uptake in these regions.

Conclusions Acute morphine treatment causes regionally specific changes in FDG uptake that parallel the lasting decrements observed after sub-chronic treatment.

Research Support Supported by DOD PR02620 and NIH R01-DA0252