Detection of pharmacologically mediated changes in cerebral activity by functional magnetic resonance imaging: the effects of sulpiride in the brain of the anaesthetised rat.
Blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was used to study the effects of the D(2)-like receptor selective antagonist, sulpiride, at 2 Tesla in the brain of the alpha-chloralose anaesthetised rat. Region of interest (ROI) analysis indicated significant (P<0.05) bilateral increases in BOLD signal intensity in the frontal cortex following a single administration of sulpiride (10 mg/kg i.v.). BOLD signal changes were slow in onset and increased gradually during the experiment, reaching 8.0+/-0.5% (mean+/-S.E.M.) above pre-injection control values 165 min after drug administration. Signal increases remained high at the experiment end (3 h post sulpiride administration). Sulpiride (30 mg/kg i.v.) had a similar effect in the frontal cortex, increasing signal 5.2+/-1.8% above control values by 174 min; its effects were, however, more variable between rats, and were not statistically significant. Sulpiride (3 mg/kg i.v.) had no significant effect upon BOLD signal intensity in any brain region. No dose of sulpiride resulted in any significant BOLD signal changes in the striatum or cerebellum. These data are supportive of the notion that sulpiride causes an increase in frontal dopaminergic function by antagonism of presynaptically located dopamine D(2) receptors in this brain region, consistent with its therapeutic action. Furthermore, the utility of BOLD contrast fMRI as a means of detecting changes in neuronal activity contingent upon the administration of a psychoactive pharmacological agent has been demonstrated.
Preece
M
M
Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge Clinical School, University Forvie Site, Robinson Way, Cambridge CB2 2PZ, UK.
Mukherjee
B
B
Huang
C L
CL
Hall
L D
LD
Leslie
R A
RA
James
M F
MF
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001931:Brain Mapping; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects* / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology*
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D004298:Dopamine