Acute dopamine D1 and D2 receptor stimulation does not modulate mismatch negativity (MMN) in healthy human subjects

Rationale Schizophrenia is commonly associated with an impairment in pre-attentive change detection, as represented by reduced mismatch negativity (MMN), an auditory event related potential. While the neurochemical basis of MMN has been linked to the integrity of the glutamatergic system involving N-methyl-D-aspartate (NMDA) receptors, the role of the dopaminergic system and in particular, the role of D-1 and D-2 receptors on MMN is yet to be determined. Objectives The aim of the present project was to investigate the acute effects of dopamine D-2 (bromocriptine) and D-1/D-2 (pergolide) receptor stimulation on the human MMN in healthy subjects. Methods Fifteen healthy male subjects participated in a double-blind, placebo-controlled, cross-over design in which each subject was tested under three acute treatment conditions separated by a 1-week wash out period; placebo, bromocriptine (2.5 mg) and pergolide (0.1 mg). The subjects were exposed to a duration-MMN paradigm with 50 ms standard tones (91%) and 100 ms deviant tones (9%). Results The results showed that neither D-2 receptor stimulation with bromocriptine, nor simultaneous D-1 and D-2 receptor stimulation with pergolide, modulated MMN. Conclusions These findings suggest that acute D-1 and D-2 receptor stimulation does not modulate MMN. While the role of dopamine cannot be completely ruled out, the findings support the view that the aberrant MMN reported in schizophrenia may be linked primarily to glutamate dysfunction involving NMDA receptors.