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 inschizophrenia 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 twoseparate 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 werecomparable 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.

[1]  A J Heritch,et al.  Dopamine in schizophrenia. , 2006, The American journal of psychiatry.

[2]  Bob Oranje,et al.  Modulating sensory gating in healthy volunteers The effects of ketamine and haloperidol , 2002, Biological Psychiatry.

[3]  R. Kahn,et al.  Effects of Typical and Atypical Antipsychotics on the Prepulse Inhibition of the Startle Reflex in Patients With Schizophrenia , 2002, Journal of clinical psychopharmacology.

[4]  M. Geyer,et al.  Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype? , 2002, The American journal of psychiatry.

[5]  N. Swerdlow,et al.  Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies , 2002, Psychopharmacology.

[6]  T. Sharma,et al.  Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication. , 2000, Archives of general psychiatry.

[7]  D L Braff,et al.  Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. , 2000, The American journal of psychiatry.

[8]  F. Larøi Schizophrenia from a neurocognitive perspective: probing the impenetrable darkness , 2000 .

[9]  H. Sackeim,et al.  Amphetamine disrupts P50 suppression in normal subjects , 1999, Biological Psychiatry.

[10]  R. Tandon,et al.  Antipsychotics from theory to practice: integrating clinical and basic data. , 1999, The Journal of clinical psychiatry.

[11]  T. Sharma,et al.  Normalization of information processing deficits in schizophrenia with clozapine. , 1999, The American journal of psychiatry.

[12]  G. Duncan,et al.  An integrated view of pathophysiological models of schizophrenia , 1999, Brain Research Reviews.

[13]  Bob Oranje,et al.  P50 suppression and prepulse inhibition of the startle reflex in humans: a correlational study , 1999, Biological Psychiatry.

[14]  M. Martin-Iverson Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man , 1999, Journal of psychopharmacology.

[15]  C. Bradshaw,et al.  Effects of bromocriptine and haloperidol on prepulse inhibition: comparison of the acoustic startle eyeblink response and the N1/P2 auditory-evoked response in man , 1999, Journal of psychopharmacology.

[16]  K. Nuechterlein,et al.  P50 Suppression in Recent-Onset Schizophrenia: Clinical Correlates and Risperidone Effects , 1998 .

[17]  C. Bradshaw,et al.  Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man , 1998, Journal of psychopharmacology.

[18]  M. Geyer,et al.  Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects , 1998, Schizophrenia Research.

[19]  Green,et al.  Schizophrenia from a Neurocognitive Perspective: Probing the Impenetrable Darkness , 1997 .

[20]  J. P. Morgan Principles of Pharmacology: Basic Concepts and Clinical Applications , 1997 .

[21]  Brett A. Clementz,et al.  P50 Suppression among schizophrenia and normal comparison subjects: A methodological analysis , 1997, Biological Psychiatry.

[22]  P. Ward,et al.  Replication of a P50 auditory gating deficit in Australian patients with schizophrenia , 1996, Psychiatry Research.

[23]  L. Wilkins Biological Bases of Brain Function and Disease , 1995, Neurology.

[24]  J. Lamberti,et al.  Concurrent assessment of acoustic startle and auditory P50 evoked potential measures of sensory inhibition , 1993, Biological Psychiatry.

[25]  N C Andreasen,et al.  The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. , 1992, Archives of general psychiatry.

[26]  K. Davis,et al.  Dopamine in schizophrenia: a review and reconceptualization. , 1991, The American journal of psychiatry.

[27]  Robert Freedman,et al.  Elementary neuronal dysfunctions in schizophrenia , 1991, Schizophrenia Research.

[28]  Robert Freedman,et al.  Gating of auditory response in schizophrenics and normal controls Effects of recording site and stimulation interval on the P50 wave , 1991, Schizophrenia Research.

[29]  M. V. Nelson,et al.  Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine , 1990, Clinical pharmacology and therapeutics.

[30]  D L Braff,et al.  Sensorimotor gating and schizophrenia. Human and animal model studies. , 1990, Archives of general psychiatry.

[31]  R. Dempski,et al.  Pharmaceutical design and development of a Sinemet controlled-release formulation. , 1989, Neurology.

[32]  M. Galloway,et al.  Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. , 1989, Neurology.

[33]  K C Yeh,et al.  Pharmacokinetics and bioavailability of Sinemet CR: a summary of human studies. , 1989, Neurology.

[34]  Robert Freedman,et al.  Sensory gating in schizophrenics and normal controls: Effects of changing stimulation interval , 1989, Biological Psychiatry.

[35]  J. Dobkin,et al.  Cerebral vasocapacitance and TIAs , 1989, Neurology.

[36]  R Freedman,et al.  Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. , 1982, Biological psychiatry.

[37]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[38]  A. Mcghie,et al.  Disorders of attention and perception in early schizophrenia. , 1961, The British journal of medical psychology.

[39]  J. Drewe,et al.  Differential effect of food on kinetics of bromocriptine in a modified release capsule and a conventional formulation , 2004, European Journal of Clinical Pharmacology.

[40]  K H Nuechterlein,et al.  P50 suppression in recent-onset schizophrenia: clinical correlates and risperidone effects. , 1998, Journal of abnormal psychology.

[41]  H. Westenberg,et al.  Advances in the neurobiology of schizophrenia , 1995 .

[42]  P. Molinoff,et al.  Biological Bases of Brain Function and Disease , 1994 .

[43]  J. Kenemans,et al.  Removal of the ocular artifact from the EEG: a comparison of time and frequency domain methods with simulated and real data. , 1991, Psychophysiology.

[44]  P. Venables,et al.  INPUT DYSFUNCTION IN SCHIZOPHRENIA. , 1964, Progress in experimental personality research.

[45]  B. Maher,et al.  Progress in experimental personality research , 1964 .