Lack of improvement in odor identification by levodopa in humans

Several animal studies demonstrated that olfaction is modulated by dopamine (DA). We examined if such results could be replicated in humans. Thus, we tested olfaction in elderly healthy humans before and after external administration of levodopa in a double-blind, placebo-controlled, randomized cross-over study. Main outcome measure was the sum of correctly identified odors in an odor identification paradigm. In contrast to what had been demonstrated in rats, levodopa did not improve olfaction. We even noted a trend for the reverse. Blood pressure, mood ratings, as well as performance in a simple motor task were comparable between conditions, indicating that levodopa did not induce differences in general arousal, mood, attention, or reaction time. Our findings may be explained by differences in the distribution of dopaminergic receptor subtypes in the olfactory system in animals and humans, by relative differences in dosing regimes, or by subtle differences in the respective paradigms. These hypotheses have to be tested in future experiments, but our study demonstrates that results from animal studies cannot be directly transferred to the human situation.