Steady-state and the epistemology of dopamine metabolism

The steady-state is defined as the condition of equilibrium between the rates of formation and elimination of a substance in a particular compartment. This occurs when the chickens in Figure 3.3 reach a constant size. In the strict sense, the steady-state is necessarily a hypothetical condition, since the concentration of any substance in the brain can fluctuate with time. The rate of increase in the concentration of DOPA after blockade of AAADC was introduced as an approach to calculating steady-state dopamine synthesis, but subject to the caveats that decarboxylation is not the unique fate of DOPA formed in the brain, and that the pharmacological treatment can itself perturb the steady-state. The trace amines tyramine and phenylethylamine present another instance of steady-state calculations; the lack of a secure storage compartment for these compounds results in very rapid metabolism by MAO, such that the steady-state concentrations in rat brain are very low relative to the amount of dopamine. However, there is a linear and substantial increase in their concentrations during several hours after blockade of MAO with pargyline (Durden & Philips 1980). That this process remains linear with time suggests that their accumulation does not modulate their own rate of synthesis. In contrast, the accumulation of dopamine in the brain is linear only for the initial 15 min after blockade of MAO, reflecting the more responsive feedback mechanisms in neurotransmitter synthesis (Venero, Machado, & Cano 1991).