Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.

OBJECTIVES: After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty. METHODS: Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain. RESULTS: In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time. CONCLUSIONS: NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.

Rapid decay of cocaine-induced behavioral sensitization of locomotor behavior.

Sprague Dawley rats received three daily intraperitoneal (i.p.) injections of saline or 15 mg/kg cocaine. Following an interval of 2, 5 or 8 days, the behavioral response of separate groups of rats to a challenge injection of cocaine (15 mg/kg) was tested in an open field. After repeated cocaine (15 mg/kg) injection, movement in both the vertical and horizontal plane was increased in cocaine-treated rats 2, but not 5 or 8, days after treatment as compared to saline-treated subjects. In addition, behavioral ratings along an ordinal scale designed to reflect increases in behavioral activation were increased in cocaine-treated rats 2, but not 5 or 8, days after treatment. These results stand in contrast to other reports demonstrating long-lasting neural and behavioral changes after similar treatment regimens. Taken together, the results suggest that a treatment regimen of 15 mg/kg per day of cocaine for 3 days produces behavioral sensitization of locomotor behavior; however, this cocaine-induced behavioral sensitization does not persist beyond a few (< 5) days after repeated cocaine treatment, using the current experimental parameters.