Alterations in local cerebral glucose utilization in rats after chronic amphetamine administration without subsequent challenge

Abstract

The 2-deoxyglucose (2-DG) method was used to study regional metabolic changes in rats following chronic d-amphetamine treatment without subsequent challenges. Four groups of rats were pretreated (intraperitoneal administration) with d-amphetamine (0, 1, 5, or 10 mg/kg) once per day for 14 days. After a 7-day abstinence period without further challenge, the 2-DG method was used to measure the rates of local cerebral glucose utilization (LCGU). Significant metabolic changes among the four groups were found in five brain regions, including the nucleus accumbens and the lateral habenular nucleus. Another four groups of rats with the same pretreatment regimens, challenged with 5 mg/kg d-amphetamine, were used for behavioral testing. The results showed intense stereotyped behaviors in the 5 mg/kg and the 10 mg/kg groups. In the steady state, however, there were no significant glucose utilization changes in the nigrostriatal system, which is thought to be related to stereotyped behaviors. During steady state, metabolic changes were found in a limited number of brain regions. No difference in LCGU was found in the sensitization-related regions. Further challenges with stimulants may be necessary to investigate the metabolic responses after sensitization.