No effects of l-dopa and bromocriptine on psychophysiological parameters of human selective attention.
Patients with schizophrenia exhibit diverse cognitive deficits, one of which is a loss of the ability to focus attention. According to the revised dopamine hypothesis of schizophrenia both an increased mesolimbic and a decreased prefrontal dopaminergic activity is suggested to be involved in schizophrenia. The current study was designed to explore the relationship between dopamine and two psychophysiological parameters of selective attention, i.e. P300 amplitude and processing negativity (PN) in healthy volunteers. In two separate experiments, with a double-blind, balanced and placebo-controlled crossover design, 18 healthy male volunteers were orally administered either 300 mg l-dopa (precursor of dopamine) or placebo (experiment I), or 1.25mg bromocriptine (D2 agonist) or placebo (experiment II). Following this treatment they were tested in an auditory, dichotic selective attention paradigm. An increase in P300 amplitude was found following deviant stimuli when compared to standard stimuli and following attended stimuli when compared to unattended stimuli, regardless of treatment. Similarly, PN was found regardless of treatment. Neither l-dopa nor bromocriptine affected task performance or the amplitudes of PN or P300. In the present study neither l-dopa nor bromocriptine affected PN, P300 amplitude or task performance in healthy controls, phenomena which are usually found to be disrupted in schizophrenia. This indicates that P300 amplitude and PN are neither affected by a global (l-dopa) increased dopaminergic activity, nor by a more selectively towards striatal areas targeted (bromocriptine) increase in dopaminergic activity.
Oranje
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Centre for Neuropsychiatric Schizophrenia Research, Department of Psychiatry, Bispebjerg University Hospital, Copenhagen, Denmark. B.Oranje@cnsr.dk
Gispen-de Wied
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Westenberg
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Kemner
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Verbaten
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Kahn
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D000328:Adult; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects*; D001971:Bromocriptine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D004585:Electrooculography; D018913:Event-Related Potentials, P300 / Q000187:drug effects; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000097:blood; D011597:Psychomotor Performance / Q000187:drug effects; D011603:Psychophysiology; D017448:Receptors, Dopamine D2 / Q000819:agonists
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D007980:Levodopa; D011388:Prolactin; D004298:Dopamine; D006719:Homovanillic Acid