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

Abstract

Summary1. Spontaneous locomotor activity (activity) in male Wistar rats was compared with the concentrations of brain noradrenaline (NA), dopamine (DA) and metaraminol. 2. a-Methyl-m-tyrosine (aMMT) (400 mg/kg) reduced the concentrations of DA as well as NA but activity remained high in the presence of metaraminol formed from the aMMT. When tetrabenazine (TBZ) was given after aMMT pretreatment there was a fall in the levels of activity and in the concentrations of NA, DA and metaraminol.3. a-Methyl-p-tyrosine (aMT) 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 aMT and TBZ, administration of L-dopa produced a return in activity which was significantly correlated with the concentration of NA but not DA. When aMMT 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 13 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 aMT 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. IntroductionOur investigations (Chan & Webster, 1971) have suggested that the method by which a drug depletes the central nervous system of catecholamines may determine whether or not it reduces activity. Thus, although both a-methyl-m-tyrosine and tetrabenazine caused a comparable depletion of brain noradrenaline in the rat, at