Systemic sulpiride modulates striatal blood flow: relationships to spatial working memory and planning

TY - JOUR

T1 - Systemic sulpiride modulates striatal blood flow

T2 - relationships to spatial working memory and planning

AU - Mehta, Mitul A

AU - McGowan, Stephen W

AU - Lawrence, Andrew D

AU - Aitken, Michael R F

AU - Montgomery, Andrew J

AU - Grasby, Paul M

PY - 2003/12

Y1 - 2003/12

N2 - The dopamine D2 receptor antagonist sulpiride can produce a range of cognitive deficits in normal volunteers, consistent with those seen in Parkinson's disease (PD). This, together with studies in experimental animals, implies sulpiride might be acting in the striatum. However, subtle changes in prefrontal cortex (PFC) activity are seen following L-Dopa withdrawal in PD during working memory tasks, suggesting that this may be a further site of action for dopamine D2 receptor antagonists. We have investigated the effects of sulpiride within the PFC and striatum in normal male volunteers. In two separate experiments, using identical PET regional cerebral blood flow (rCBF) methods, a combined drug and psychological challenge was performed, utilising working memory and planning tasks, and oral sulpiride 400 mg and placebo. Data were analysed using SPM99. Sulpiride increased striatal rCBF bilaterally and the working memory and planning tasks activated discrete frontoparietal networks in keeping with previous studies. However, for the working memory tasks, no changes in performance or task-induced rCBF were observed after sulpiride. For the planning task, improved performance was seen on sulpiride. Also, sulpiride attenuated striatal activity during planning (as assessed using a small volume correction, P<0.05 corrected), and this attenuation was related to performance changes. These findings suggest that (1) sulpiride produces clear increases in striatal rCBF, (2) in contrast to previous studies no effects of sulpiride on performance of the working memory tasks or the associated neural networks were observed, and (3) sulpiride may modulate performance of more complex cognitive tasks via alterations in striatal neural activity.

AB - The dopamine D2 receptor antagonist sulpiride can produce a range of cognitive deficits in normal volunteers, consistent with those seen in Parkinson's disease (PD). This, together with studies in experimental animals, implies sulpiride might be acting in the striatum. However, subtle changes in prefrontal cortex (PFC) activity are seen following L-Dopa withdrawal in PD during working memory tasks, suggesting that this may be a further site of action for dopamine D2 receptor antagonists. We have investigated the effects of sulpiride within the PFC and striatum in normal male volunteers. In two separate experiments, using identical PET regional cerebral blood flow (rCBF) methods, a combined drug and psychological challenge was performed, utilising working memory and planning tasks, and oral sulpiride 400 mg and placebo. Data were analysed using SPM99. Sulpiride increased striatal rCBF bilaterally and the working memory and planning tasks activated discrete frontoparietal networks in keeping with previous studies. However, for the working memory tasks, no changes in performance or task-induced rCBF were observed after sulpiride. For the planning task, improved performance was seen on sulpiride. Also, sulpiride attenuated striatal activity during planning (as assessed using a small volume correction, P<0.05 corrected), and this attenuation was related to performance changes. These findings suggest that (1) sulpiride produces clear increases in striatal rCBF, (2) in contrast to previous studies no effects of sulpiride on performance of the working memory tasks or the associated neural networks were observed, and (3) sulpiride may modulate performance of more complex cognitive tasks via alterations in striatal neural activity.

KW - Adult

KW - Antidepressive Agents, Second-Generation

KW - Cerebrovascular Circulation

KW - Decision Making

KW - Humans

KW - Image Interpretation, Computer-Assisted

KW - Male

KW - Memory, Short-Term

KW - Neostriatum

KW - Neuropsychological Tests

KW - Psychomotor Performance

KW - Space Perception

KW - Sulpiride

KW - Tomography, Emission-Computed

U2 - 10.1016/j.neuroimage.2003.08.007

DO - 10.1016/j.neuroimage.2003.08.007

M3 - Article

C2 - 14683704

SN - 1053-8119

VL - 20

SP - 1982

EP - 1994

JO - NeuroImage. Clinical

JF - NeuroImage. Clinical

IS - 4

ER -