SPECT imaging of striatal dopamine release after amphetamine challenge.
This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sulfate (d-amphetamine) challenge testing.


METHODS
A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subjects first underwent a controlled experiment to demonstrate that stable levels of striatal and occipital activities could be maintained from 150 to 420 min during programmed infusion of the tracer. Next, seven subjects underwent the experiment with d-amphetamine. The experimental conditions were identical except that 0.3 mg/kg amphetamine was injected intravenously at 240 min. The behavioral effects of d-amphetamine were measured by self-rating on the following analog scales: euphoria, alertness, restlessness and anxiety.


RESULTS
The d-amphetamine injection induced a 15% +/- 4% (mean +/- s.d.) decrease in D2 receptor availability, measured as the specific-to-nonspecific equilibrium partition coefficient (V3"). The d-amphetamine injection induced marked increase in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availability measured with SPECT. In contrast, the anxiety response was milder and not correlated with the decrease in D2 availability.


CONCLUSIONS
These studies demonstrate the feasibility of using [123I]IBZM programmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correlates of emotions.
Laruelle
M
M
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Abi-Dargham
A
A
van Dyck
C H
CH
Rosenblatt
W
W
Zea-Ponce
Y
Y
Zoghbi
S S
SS
Baldwin
R M
RM
Charney
D S
DS
Hoffer
P B
PB
Kung
H F
HF
D000293:Adolescent; D000328:Adult; D001519:Behavior / Q000187:drug effects; D001549:Benzamides; D001794:Blood Pressure / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011759:Pyrrolidines; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D003913:Dextroamphetamine; D004298:Dopamine