Effects of acute metabolic stress on striatal dopamine release in healthy volunteers.
Several lines of evidence indicate that a variety of metabolic stressors, including acute glucose deprivation are associated with dopamine release. Pharmacologic doses of the glucose analogue, 2-deoxyglucose (2DG) cause acute glucoprivation and are associated with enhanced dopamine turnover in preclinical studies. In this study, we utilized [11C]raclopride PET to examine 2DG-induced striatal dopamine release in healthy volunteers. Six healthy volunteers underwent PET scans involving assessment of 2DG-induced (40 mg/kg) decrements in striatal binding of the D(2)/D(3) receptor radioligand [11C]raclopride. Decreases in [11C]raclopride specific binding reflect 2DG-induced changes in synaptic dopamine. Specific binding significantly decreased following 2DG administration, reflecting enhanced synaptic dopamine concentrations (p =.02). The administration of 2DG is associated with significant striatal dopamine release in healthy volunteers. Implications of these data for investigations of the role of stress in psychiatric disorders are discussed.
Adler
C M
CM
Experimental Therapeutics Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA.
Elman
I
I
Weisenfeld
N
N
Kestler
L
L
Pickar
D
D
Breier
A
A
D000328:Adult; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D006801:Humans; D008297:Male; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D010865:Pilot Projects; D020891:Raclopride / Q000008:administration & dosage; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011954:Receptors, Dopamine; D020891:Raclopride; D003847:Deoxyglucose; D005947:Glucose; D004298:Dopamine