Differences in norepinephrine and dopamine neurotransmitter storage systems.

Low doses of d-amphetamine (d-AMP) produced a 50% or greater decrease in the firing rates of both dopamine (DA) neurons (substantia nigra zone compacta) and norepinephrine (NE) neurons (locus coeruleus). However, pretreatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT) blocked the d-AMP-induced reduction in DA neuron firing rate, but had no effect on the d-AMP-induced reduction in NE cell firing rate. Similarly, alpha-MT administered subsequent to d-AMP readily reversed the d-AMP-induced decrease in the firing rates of DA cells, but caused no significant reversal in NE cell firing rates. These electrophysiological findings, in conjunction with biochemical and behavioral data, support the hypothesis that there is a difference in the DA and NE neurotransmitter storage mechanism. In the DA neuron, there appears to be a slow transfer between stored and readily-releasable (newly synthesized) amine pools so that, following synthesis inhibition, there is little DA available for release. However, in the NE neuron, there is a more rapid mobilization of stored amine to readily releasable sites, such that d-AMP continues to cause the release of NE even though synthesis of transmitter is blocked.