Central nervous system noradrenergic and dopaminergic turnover in response to acute neuroleptic challenge.
The objective of this study was to obtain direct neurochemical measures of the central nervous system's response to a typical neuroleptic, haloperidol, in human subjects. Nine healthy volunteers participated in this study. Central nervous system neuronal activity was assessed by measuring the plasma concentration and overflow from the brain of dopamine, norepinephrine, and their lipophilic and acidic metabolites after acute intravenous administration of haloperidol. By combining bilateral internal jugular vein blood sampling with cerebral blood flow scans we were able to differentiate between cortical and subcortical responses to haloperidol. The central nervous system response to haloperidol administration displayed a degree of regional specificity. Dopamine release, estimated from the overflow of homovanillic and dihydroxyphenylacetic acids, was reduced in cortical but not subcortical brain regions. Norepinephrine turnover was increased in cortical and subcortical brain regions. The overflow of homovanillic acid from the brain into the internal jugular veins was not related quantitatively to the arterial plasma concentrations of the catecholamines examined, homovanillic and dihydroxyphenylacetic acids or prolactin. Measurements of catecholamines and their metabolites in arterial plasma gave little indication as to monoaminergic neuronal activity in the brain.
Lambert
G W
GW
Human Autonomic Function Laboratory, Baker Medical Research Institute, Prahran Victoria, Australia.
Horne
M
M
Kalff
V
V
Kelly
M J
MJ
Turner
A G
AG
Cox
H S
HS
Jennings
G L
GL
Esler
M D
MD
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*
D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid