Imaging Human Mesolimbic Dopamine Transmission With Positron Emission Tomography. Part II: Amphetamine-Induced Dopamine Release in the Functional Subdivisions of the Striatum

Abstract

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3") was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (DeltaV3") in limbic (ventral striatum, -15.3 +/- 11.8%) and sensorimotor (postcommissural putamen, -16.1 +/- 9.6%) regions compared with associative regions (caudate and precommissural putamen, -8.1 +/- 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in DeltaV3" between limbic (-17.8 +/- 13.8%), sensorimotor (-16.6 +/- 9.9%), and associative regions (-7.5 +/- 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger DeltaV3" in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

“…To our knowledge, these results provide the first evidence that APTD decreases stimulated DA release in human brain. The effect of APTD on d-amphetamine-induced changes in striatal [ 11 C]raclopride BP was restricted to limbic and associative subcompartments, as defined by Laruelle, Haber, and co-workers (Haber and McFarland, 1999;Mawlawi et al, 2001;Martinez et al, 2003). This agrees with previous observations that d-amphetamine preferentially decreases [ 11 C]raclopride BP in these regions (Drevets et al, 2001; Leyton et al, 2002;Martinez et al, 2003).…”

“…The effect of APTD on d-amphetamine-induced changes in striatal [ 11 C]raclopride BP was restricted to limbic and associative subcompartments, as defined by Laruelle, Haber, and co-workers (Haber and McFarland, 1999;Mawlawi et al, 2001;Martinez et al, 2003). This agrees with previous observations that d-amphetamine preferentially decreases [ 11 C]raclopride BP in these regions (Drevets et al, 2001; Leyton et al, 2002;Martinez et al, 2003). Animal studies suggest that this reflects regional differences in drug-induced increases in synaptic DA levels (Di Chiara and Imperato, 1988) rather than an artifact of the PET method.…”

“…Second, the striatum was delineated from a probabilistic brain atlas (Collins et al, 1994a). Third, the study's ROI were drawn within the striatum's boundaries, based on the functional organization of limbic, associative, and sensory motor subcompartments as proposed by Laruelle, Haber, and co-workers (Haber and McFarland, 1999;Mawlawi et al, 2001;Martinez et al, 2003) ( Figure 1): ventral striatum (limbic striatum), precommissural dorsal caudate (posterior caudate/associative striatum), precommissural dorsal putamen (posterior putamen/associative striatum), postcommissural caudate (anterior caudate/associative striatum), and postcommissural putamen (anterior putamen/sensory motor putamen). The ROI were drawn on each subject's MRI to match their individual neuroanatomy, and the same regions were used for both the first and second scans.…”

Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking

“…Conventional PET analysis methods are not well-suited to the capture of transient neurotransmitter events 25,29 . We have characterized the shortcomings of various conventional analyses using simulation studies and human data 30 .…”

“…This is the area of the brain that is implicated in drug addiction. Following Martinez et al 25 apply a mask of the pre-commissural striatum (ventral striatum, dorsal caudate, dorsal putamen) to all the PET data in template space.…”