Selectivity of release of norepinephrine, dopamine and 5-hydroxytryptamine by amphetamine in various regions of rat brain

Tissues from various regions of rat brain were incubated with [ 3H]norepinephrine, [ 3H]dopamine or [ 3H]5-hydroxytryptamine; excess amine was washed from the tissues and the [ 3H]amines present in the incubation medium and tissues were measured. The release of the accumulated [ 3H]amine by amphetamine was related to the nature of the neurons in the several regions and the release of each of the [ 3H]amines was quite selective for neurons which contain the corresponding endogenous amine. The release of [ 3H]norepinephrine from norepinephrine neurons is most sensitive to amphetamine, while the release of [ 3H]dopamine from dopamine neurons requires higher concentrations of amphetamine. Release of [ 3H]5-hydroxytryptamine from 5-hydroxytryptamine neurons appears to be least sensitive to amphetamine. This selective effect of amphetamine on neurons containing biogenic amines may help to explain the behavioral changes which occur at different doses of amphetamine. The selectivity of release of the [ 3H]-amines was also examined by observing the accumulation and release of [ 3H]norepinephrine and [ 3H]5-hydroxytryptamine in the presence of five-fold higher concentrations of the unlabeled amines. There was relatively little effect of unlabeled norepinephrine on the accumulation and release of [ 3H]5-hydroxytryptamine or of unlabeled 5-hydroxytryptamine on [ 3H]norepinephrine accumulation and release. Unlabeled dopamine reduced the accumulation and altered the release of [ 3H]norepinephrine and [ 3H]5-hydroxytryptamine, but this was much less marked than the effect of the unlabeled analogues of the [ 3H]amines. The release of each of the [ 3H]amines by its unlabeled analogue occurred with concentrations as low as, or lower than, the release produced by amphetamine or the other unlabeled amines. The release of the [ 3H]amines by a five-fold higher concentration of the unlabeled analogues was so high that it was not increased further by very high concentrations of amphetamine (10 −3 M). These results suggest that, under the conditions of this study, the [ 3H]amines are accumulated within specific neurons of brain tissue and that they are selectively released by amphetamine.