Brain Changes with Lithium and Haloperidol: An Animal Study

Psychopharmacy has been linked to changes in gray-matter volumes, but controlled experiments of this effect cannot easily be done on humans because of ethical problems, including long periods on placebo, and variations in age at onset, duration, and severity of illness. Therefore, these researchers examined this link in late-adolescent rats. Rats were infused with haloperidol (high- or low-dose), lithium, or vehicle for 8 weeks, with doses selected to achieve human equivalents of 65% to 90% dopamine D₂ receptor occupancy for haloperidol and 0.4 to 1.2 mEq/L for lithium blood levels.

All animals gained weight, but only haloperidol-treated rats showed stereotypical movements. On magnetic resonance imaging, postinfusion cortical gray matter and…