Baseline and amphetamine-stimulated dopamine activity are related in drug-naïve schizophrenic subjects.
BACKGROUND
Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC).


METHODS
Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP(ND)) for striatal D2 at baseline, after amphetamine administration and after DA depletion.


RESULTS
Amphetamine induced decrease in BP(ND) was positively correlated with BP(ND) increase after DA depletion in SCZ (p = .02) but not in HC (p = .44). Additionally, both were significantly increased.


CONCLUSIONS
In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the alpha-methyl-para-tyrosine (alpha MPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity.
Abi-Dargham
Anissa
A
Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. aa324@columbia.edu
van de Giessen
Elsmarieke
E
Slifstein
Mark
M
Kegeles
Lawrence S
LS
Laruelle
Marc
M
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D001549:Benzamides; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D055815:Young Adult; D019805:alpha-Methyltyrosine
D001549:Benzamides; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D019805:alpha-Methyltyrosine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D000661:Amphetamine; D004298:Dopamine