Social withdrawal and gambling-like profile after lentiviral manipulation of DAT expression in the rat accumbens

Adriani, Walter; Boyer, Frederic; Leo, Damiana; Canese, Rossella; Podo, Franca; Perrone-Capano, Carla; Dreyer, Jean-Luc; Laviola, Giovanni

doi:10.1017/S1461145709991210

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Journal article

Social withdrawal and gambling-like profile after lentiviral manipulation of DAT expression in the rat accumbens

Adriani, Walter Sections of Behavioral Neuroscience and of Molecular & Cellular Imaging, Department Cell Biology & Neurosciences, Istituto Superiore di Sanità, Roma, Italy
Boyer, Frederic Department of Medicine, University of Fribourg, Switzerland
Leo, Damiana Institute of Genetics and Biophysics, CNR, Naples, Italy
Canese, Rossella Sections of Behavioral Neuroscience and of Molecular & Cellular Imaging, Department Cell Biology & Neurosciences, Istituto Superiore di Sanità, Roma, Italy
Podo, Franca Sections of Behavioral Neuroscience and of Molecular & Cellular Imaging, Department Cell Biology & Neurosciences, Istituto Superiore di Sanità, Roma, Italy
Perrone-Capano, Carla Institute of Genetics and Biophysics, CNR, Naples, Italy - Department of Biological Sciences, University of Naples, Italy
Dreyer, Jean-Luc Department of Medicine, University of Fribourg, Switzerland
Laviola, Giovanni Sections of Behavioral Neuroscience and of Molecular & Cellular Imaging, Department Cell Biology & Neurosciences, Istituto Superiore di Sanità, Roma, Italy

30.11.2009

Published in:

The International Journal of Neuropsychopharmacology. - 2010, vol. 13, no. 10, p. 1329-1342

English Dysfunction of brain dopamine transporter (DAT) has been associated with sensation seeking and impulse-control disorders. We recently generated a new animal model by stereotaxical inoculation of lentiviral vectors, which allowed localized intra-accumbal delivery of modulators for DAT gene: GFP (green fluorescent protein) control, silencers (Sil), a regulatable enhancer (DAT+), or both (DAT+Sil). Wistar male rats were followed both for socio-emotional profiles and for propensity to seek risky, uncertain rewards. Elevated anxiety and affiliation towards an unfamiliar partner emerged in Sil rats. Interestingly, in DAT+Sil rats (and Sil rats to a lesser extent) levels of playful social interaction were markedly reduced compared to controls. These DAT+Sil rats displayed a marked ‘gambling-like’ profile (i.e. preference for a large/uncertain over a small/sure reward), which disappeared upon doxycycline-induced switch-off onto DAT enhancer, but consistently reappeared with doxycycline removal. MRI-guided ¹H-MRS (at 4.7 T) examinations in vivo (under anaesthesia) revealed changes in the bioenergetic metabolites (phosphocreatine and total creatine) for DAT+Sil rats, indicating a functional up-regulation of dorsal striatum (Str) and conversely a down-regulation of ventral striatum (i.e. nucleus accumbens, NAc). A combined profile of (1) enhanced proneness to gambling and (2) strong social withdrawal is thus associated with altered DAT-induced balance within forebrain dopamine systems. In fact, risk of developing a gambling-prone, social-avoidant psychopathology might be associated with (1) dominant semi-automatic strategies and/or habits, developed within Str circuits, and (2) reduced NAc function, with poorer feedback adjustment on decisions by aversive experiences.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language