Dopaminergic modulation of rapid reality adaptation in thinking.
Dopamine has long held a prominent role in the interpretation of schizophrenia and other psychoses. Clinical studies on confabulation and disorientation, disorders marked by a confusion of reality in thinking, indicated that the ability to keep thinking in phase with reality depends on a process suppressing the interference of upcoming memories that do not refer to ongoing reality. A host of animal studies and a recent clinical study suggested that this suppression might correspond to the phasic inhibition of dopaminergic neurons in response to the absence of expected outcomes. In this study, we tested healthy subjects with a difficult version of a memory paradigm on which confabulating patients had failed. Subjects participated in three test sessions, in which they received in double-blind, randomized fashion L-dopa, risperidone, or placebo. We found that l-dopa, in comparison with risperidone, impaired performance in a highly specific way, which corresponded to the pattern of patients with reality confusion. Specifically, they had an increase of false positive responses, while overall memory performance and reaction times were unaffected. We conclude that dopaminergic transmission influences the ability to rapidly adapt thinking to ongoing reality.
Schnider
A
A
Division of Neurorehabilitation, Department of Clinical Neurosciences, University Hospitals and University of Geneva, Geneva, Switzerland. armin.schnider@hcuge.ch
Guggisberg
A
A
Nahum
L
L
Gabriel
D
D
Morand
S
S
D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology; D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004311:Double-Blind Method; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008606:Mental Processes / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011605:Psychoses, Substance-Induced / Q000378:metabolism* / Q000503:physiopathology; D018967:Risperidone / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D007980:Levodopa; D018967:Risperidone; D004298:Dopamine