What proportion of striatal D2 receptors are occupied by endogenous dopamine at baseline? A meta-analysis with...

Using molecular imaging techniques - positron emission tomography (PET) and single-photon emission computed tomography (SPECT) - in conjunction with an acute dopamine depletion challenge (alpha-methyl-para-tyrosine) it is possible to estimate endogenous dopamine levels occupying striatal dopamine D₂ receptors (D₂R) in humans in vivo. However, it is unclear what proportion of striatal D₂R are occupied by endogenous dopamine under normal conditions. This is important since it has been suggested that in schizophrenia there may be a substantial proportion of striatal D₂R which are occupied by endogenous dopamine and not accessible by therapeutic doses of antipsychotics. In order to clarify these issues, we conducted a meta-analysis of dopamine depletion studies using substituted benzamide radiotracers in healthy persons. This meta-analysis suggests that anywhere from 8 to 21% (weighted average 11%) of striatal D₂R may be occupied by endogenous dopamine at baseline. Using these estimates, we propose an updated occupancy model and tentatively suggest that antipsychotics inhibit a smaller proportion of the total pool of striatal D₂R in vivo than previously acknowledged. This article is part of the issue entitled 'Special Issue on Antipsychotics'.