Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson's disease.
BACKGROUND
The mesotelencephalic dopamine system has been implicated in cognitive processes dependent on an intact prefrontal cortex. Most previous research in humans has focused on dopaminergic agonists and their effects on tasks of working memory.


OBJECTIVE
The present study was designed to investigate the cognitive and subjective effects of two doses (200 mg and 400 mg) of the dopaminergic D(2) receptor antagonist, sulpiride on a broad range of well-validated neuropsychological tasks in a group of 34 young healthy male volunteers.


METHODS
Cognitive tasks were administered to subjects after ingestion of either drug or placebo within a double-blind, placebo-controlled, cross-over design. The cognitive tests included tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and were designed to assess visuospatial recognition memory, planning ability, working memory, strategy learning, sustained attention and attentional set-shifting. In addition, the National Adult Reading Test (NART) was used to assess verbal IQ, and visual analogue scales to assess subjective effects of the drug.


RESULTS
Subjects on sulpiride were impaired on the tasks of spatial recognition, spatial working memory (sequence generation), planning (one-touch Tower of London) and attentional set-shifting. Only the spatial working memory task demonstrated a dose dependent effect. The impairments were not due to generalised sedative or motoric influences of sulpiride.


CONCLUSIONS
All of the tasks impaired following sulpiride are known to be sensitive to frontal lobe damage and the precise pattern of deficits seen is consistent with the anatomical distribution of central dopamine receptors. The results are discussed with particular reference to their close simulation of the impairments seen in idiopathic Parkinson's disease.
Mehta
M A
MA
Department of Psychiatry, University of Cambridge, School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Sahakian
B J
BJ
McKenna
P J
PJ
Robbins
T W
TW
D000328:Adult; D000339:Affect / Q000187:drug effects; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000523:psychology*; D018592:Cross-Over Studies; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007858:Learning / Q000187:drug effects; D008297:Male; D009483:Neuropsychological Tests; D020734:Parkinsonian Disorders / Q000523:psychology*; D010364:Pattern Recognition, Visual / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology*; D011795:Surveys and Questionnaires
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D013469:Sulpiride