Is inhibition of dopamine uptake relevant to the hypnotic action of i.v. anaesthetics?

We have examined the effects of ketamine, etomidate, propofol and thiopentone on the uptake of [3H]-dopamine into rat striatal synaptosomes. [3H]-dopamine uptake (5 min, 37 degrees C) was potently inhibited by nomifensine, a classical inhibitor of the dopamine carrier. All anaesthetics induced concentration-related inhibition of the uptake process, values for IC50 being 4.6 x 10(-6), 5.5 x 10(-5), 1.5 x 10(-4) and 2.7 x 10(-4) mol litre-1 for ketamine, etomidate, propofol and thiopentone, respectively. For all anaesthetics, inhibition of [3H]-dopamine uptake was reversible with a non-competitive profile. These data suggest that inhibition of striatal dopamine uptake may represent a relevant target site for some, but not all, i.v. anaesthetics.