Increasing dopaminergic activity: effects of L-dopa and bromocriptine on human sensory gating.
Schizophrenic patients show a loss of sensory gating, which is reflected in a reduced P50 suppression. Because most of the symptoms in schizophrenia can be reduced by antagonists of the dopaminergic (D2) system, the loss in sensory gating might be related to an increased dopaminergic activity. Therefore, in the present study, the effects of increased dopaminergic neurotransmisson on sensory gating in healthy volunteers were investigated. In a double-blind, balanced, placebo-controlled design, healthy male volunteers were challenged in two separate studies with either 300 mg L-dopa (precursor of dopamine) or placebo (n=16) and 1.25 mg bromocriptine (D2 agonist) or placebo (n=17). Subsequently, they were tested for their sensory gating (P50 suppression). P50 suppression values in the placebo condition were comparable to those found in literature. Although both L-dopa and bromocriptine reduced P50 amplitude, they did so in an equal ratio for both the response to the conditioning (C) and the testing (T) stimuli, therefore not resulting in a reduction of the P50 suppression ratio (T/C). In the present study, neither L-dopa nor bromocriptine reduced sensory gating in healthy volunteers. This suggests that an increased dopaminergic activity in humans is not responsible for the reduction in sensory gating as seen, for example, in schizophrenia.
Oranje
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Center for Neuropsychiatric Schizophrenia Research, Department of Psychiatry afd E, 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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D000161:Acoustic Stimulation; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D001971:Bromocriptine / Q000494:pharmacology*; D018592:Cross-Over Studies; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D011388:Prolactin / Q000097:blood; D012683:Sensory Deprivation; D013997:Time Factors
D015259:Dopamine Agents; D018491:Dopamine Agonists; D001971:Bromocriptine; D007980:Levodopa; D011388:Prolactin; D006719:Homovanillic Acid