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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
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    30.11.2009
Published in:
  • The International Journal of Neuropsychopharmacology. - 2010, vol. 13, no. 10, p. 1329-1342
Dopamine transporter
impulse control
in-vivo gene modulation
light/dark emersion
probabilistic delivery task
social behaviour
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
  • English
Classification
Biological sciences
License
License undefined
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Persistent URL
https://folia.unifr.ch/unifr/documents/301425
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