Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study

Midbrain dopamine (DA) neurons are not homogeneous but differ in their molecular properties and responses to external stimuli. We examined whether the modulation of excitatory synapses on DA neurons by rewarding or aversive stimuli depends on the brain area to which these DA neurons project. We identified DA neuron subpopulations in slices after injection of "Retrobeads" into single target areas of adult mice and found differences in basal synaptic properties. Administration of cocaine selectively modified excitatory synapses on DA cells projecting to nucleus accumbens (NAc) medial shell while an aversive stimulus selectively modified synapses on DA cells projecting to medial prefrontal cortex. In contrast, synapses on DA neurons projecting to NAc lateral shell were modified by both rewarding and aversive stimuli, which presumably reflects saliency. These results suggest that the mesocorticolimbic DA system may be comprised of three anatomically distinct circuits, each modified by distinct aspects of motivationally relevant stimuli. Copyright © 2011 Elsevier Inc. All rights reserved.

A method is presented for the generation of parametric images of radioligand-receptor binding using PET. The method is based on a simplified reference region compartmental model, which requires no arterial blood sampling, and gives parametric images of both the binding potential of the radioligand and its local rate of delivery relative to the reference region. The technique presented for the estimation of parameters in the model employs a set of basis functions which enables the incorporation of parameter bounds. This basis function method (BFM) is compared with conventional nonlinear least squares estimation of parameters (NLM), using both simulated and real data. BFM is shown to be more stable than NLM at the voxel level and is computationally much faster. Application of the technique is illustrated for three radiotracers: [11C]raclopride (a marker of the D2 receptor), [11C]SCH 23390 (a marker of the D1 receptor) in human studies, and [11C]CFT (a marker of the dopamine transporter) in rats. The assumptions implicit in the model and its implementation using BFM are discussed. Copyright 1997 Academic Press.

Our understanding of social anxiety disorder (also known as social phobia) has moved from rudimentary awareness that it is not merely shyness to a much more sophisticated appreciation of its prevalence, its chronic and pernicious nature, and its neurobiological underpinnings. Social anxiety disorder is the most common anxiety disorder; it has an early age of onset--by age 11 years in about 50% and by age 20 years in about 80% of individuals--and it is a risk factor for subsequent depressive illness and substance abuse. Functional neuroimaging studies point to increased activity in amygdala and insula in patients with social anxiety disorder, and genetic studies are increasingly focusing on this and other (eg, personality trait neuroticism) core phenotypes to identify risk loci. A range of effective cognitive behavioural and pharmacological treatments for children and adults now exists; the challenges lie in optimum integration and dissemination of these treatments, and learning how to help the 30-40% of patients for whom treatment does not work.