Importance of noradrenaline found in a functional pool in maintaining spontaneous locomotor activity in rats

1. Spontaneous locomotor activity (activity) in male Wistar rats was compared with the concentrations of brain noradrenaline (NA), dopamine (DA) and metaraminol.2. alpha-Methyl-m-tyrosine (alphaMMT) (400 mg/kg) reduced the concentrations of DA as well as NA but activity remained high in the presence of metaraminol formed from the alphaMMT. When tetrabenazine (TBZ) was given after alphaMMT pretreatment there was a fall in the levels of activity and in the concentrations of NA, DA and metaraminol.3. alpha-Methyl-p-tyrosine (alphaMT) produced a fall in activity which was correlated with falls in the concentrations of NA and DA. 5-Hydroxytryptamine (5-HT) did not appear to be affected.4. After depletion of NA and DA by alphaMT and TBZ, administration of L-dopa produced a return in activity which was significantly correlated with the concentration of NA but not DA. When alphaMMT was given to a similar group of pretreated animals there was no recovery of activity despite high concentrations of DA and metaraminol.5. The dopamine beta hydroxylase inhibitor, diethyldithiocarbamate (DDC), suppressed activity as well as the concentrations of NA and DA at high doses (750 mg/kg) but smaller doses (400 mg/kg) plus L-dopa gave high DA concentrations without activity.6. It is concluded that NA and not DA is associated with activity but that it is only part of the total NA which is in the biosynthetic storage granule affected by drugs like alphaMT and TBZ, which controls activity. Drugs that do not affect this pool may lower NA concentrations but not reduce activity.7. The replacement of NA by metaraminol in this functional pool does not restore activity.