Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson's disease

Rationale: The mesotelencephalic dopamine system has been implicated in cog nitive processes dependent on an intact prefrontal cortex. Most previous re search in humans has focused on dopaminergic agonists and their effects on tasks of working memory. Objectives: The present study was designed to inve stigate the cognitive and subjective effects of two doses (200 mg and 400 m g) of the dopaminergic D-2 receptor antagonist, sulpiride on a broad range of well-validated neuropsychological tasks in a group of 34 young healthy m ale volunteers. Methods: Cognitive tasks were administered to subjects afte r ingestion of either drug or placebo within a double-blind, placebo-contro lled, cross-over design. The cognitive tests included tasks from the Cambri dge 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 add ition, the National Adult Reading Test (NART) was used to assess verbal IQ, and visual analogue scales to assess subjective effects of the drug. Resul ts: Subjects on sulpiride were impaired on the tasks of spatial recognition , spatial working memory (sequence generation), planning (one-touch Tower o f London) and attentional set-shifting. Only the spatial working memory tas k demonstrated a dose dependent effect. The impairments were not due to gen eralised sedative or motoric influences of sulpiride. Conclusions: All of t he 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 dis cussed with particular reference to their close simulation of the impairmen ts seen in idiopathic Parkinson's disease.