Acute dopamine D(1) and D(2) receptor stimulation does not modulate mismatch negativity (MMN) in healthy human subjects.
BACKGROUND
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.


OBJECTIVE
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.
Leung
Sumie
S
Biological Psychiatry Research Unit, Brain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Australia.
Croft
Rodney J
RJ
Baldeweg
Torsten
T
Nathan
Pradeep J
PJ
D000161:Acoustic Stimulation / Q000379:methods; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology; D003265:Contingent Negative Variation / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D010479:Pergolide / Q000008:administration & dosage / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010479:Pergolide; D001971:Bromocriptine