Stimulant drugs trigger transient volumetric changes in the human ventral striatum

The ventral striatum (VStr) integrates mesolimbic dopaminergic and corticolimbic glutamatergic afferents and forms an essential component of the neural circuitry regulating impulsive behaviour. This structure represents a primary target of psychostimulant medication, the first-choice treatment for attention-deficit/hyperactivity disorder (ADHD), and is biochemically modified by these drugs in animals. However, the effects of stimulants on the human VStr remain to be determined. We acquired anatomical brain MRI scans from 23 never-medicated adult patients with ADHD, 31 adult patients with a history of stimulant treatment and 32 control subjects, and VStr volumes were determined using individual rater-blinded region of interest delineation on high-resolution neuroanatomical scans. Furthermore, we also extracted VStr volumes before and after methylphenidate treatment in a subsample of the medication-naïve adult patients as well as in 20 never-medicated children with ADHD. We observed smaller VStr volumes in adult patients with a history of stimulant treatment in comparison to never-medicated patients. Moreover, our longitudinal analyses uncovered a reduction of grey matter volume in the bilateral VStr in adult patients after exposure to methylphenidate, which was followed by volumetric recovery to control level. In children, the same pattern of VStr volume changes was observed after treatment with methylphenidate. These findings suggest that the altered VStr volumes previously observed in patients with ADHD may represent a transitory effect of stimulant exposure rather than an intrinsic feature of the disorder. More generally, these data show that stimulant drugs can render plastic volume changes in human VStr neuroanatomy.