Differential Patterns of Subcortical Activity Evoked by Glial GLT-1 Blockade in Prelimbic and Infralimbic Cortex: Relationship to Antidepressant-Like Effects in Rats Articles uri icon

authors

  • GASULL CAMOS, JULIA
  • SOTO MONTENEGRO, MARIA LUISA
  • CASQUERO VEIGA, MARTA
  • DESCO MENENDEZ, MANUEL
  • ARTIGAS, FRANCESC
  • CASTANE, ANNA

publication date

  • December 2017

start page

  • 988

end page

  • 993

issue

  • 12

volume

  • 20

international standard serial number (ISSN)

  • 1461-1457

electronic international standard serial number (EISSN)

  • 1469-5111

abstract

  • Background: Glutamatergic neurotransmission has emerged as a novel target in antidepressant drug development, with a critical role of the ventral anterior cingulate cortex. We recently reported that blockade of the astrocytic glutamate transporter GLT-1 with dihydrokainic acid in infralimbic cortex (rodent equivalent of ventral anterior cingulate cortex), but not in the adjacent prelimbic cortex, evoked robust antidepressant-like effects through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation and increased serotonin release. Methods: 2-deoxy-2-[F-18]-fluoro-D-glucose-positron emission tomography and computed tomography in 36 male Wistar rats microinfused bilaterally in prelimbic cortex or infralimbic cortex with dihydrokainic acid or vehicle. Results: Dihydrokainic acid microinfusion in infralimbic cortex and prelimbic cortex evoked dramatically different regional patterns of subcortical activity. In infralimbic cortex, dihydrokainic acid selectively affected midbrain areas, whereas in prelimbic cortex it affected the basal ganglia, the thalamus, and both superior and inferior colliculi. Conclusions: These results highlight the differential connectivity of infralimbic and prelimbic cortex with subcortical brain regions and support the involvement of infralimbic cortex-midbrain pathway in the antidepressant-like effects of dihydrokainic acid.

keywords

  • infralimbic; prelimbic; glutamate transporter-1; FDG-PET; dihydrokainic acid