The role of the glucocorticoid receptor from the NAcc in stress-related behaviours. Genetic dissection by viral transduction.

Abstract

L'inattivazione del gene del recettore dei glucocorticoidi nei neuroni dopaminocettivi (topi GRD1aCre) incide profondamente su alcuni comportamenti legati allo stress, tra cui le risposte comportamentali a psicostimolanti e sul ritiro sociale acquisito dopo uno stress sociale ripetute. A livello fisiologico, la mutazione del GR in neuroni postsinaptici riduce fortemente l'attività elettrica dei neuroni dopaminergici presinaptici della VTA, mostrando un ruolo del GR nella modulazione del feedback esercitata dai neuroni dopaminocettivi sui neuroni DA. Nei topi GRD1aCre, il gene GR è ricombinato in varie strutture tra cui il NACC, striato dorsale, l'amigdala e gli strati basali della corteccia, tra cui il NACC e mPFC sono noti per controllare l'attività dei neuroni DA della VTA. E 'quindi essenziale perfezionare l'identificazione delle strutture cerebrali pertinenti.

Glucocorticoid Receptor gene inactivation in dopaminoceptive neurons (GRD1aCre mice) deeply affects some stress-related behaviors, including behavioral responses to psychostimulants and social withdrawal acquired after repeated social stress. At the physiological level, the mutation of GR in post-synaptic neurons deeply reduces the electrical activity of presynaptic DA neurons of the VTA, showing a role for GR in the modulation of the feedback exerted by dopaminoceptive neurons on DA neurons. In GRD1aCre mice, GR gene is recombined in several structures including the NAcc, the dorsal striatum, the amygdala and the basal layers of the cortex, among which the NAcc and the mPFC are known to control VTA DA neurons activity. It is therefore essential to refine the identification of the relevant brain structures. My objective was to identify whether the GR in the NAcc is important for the observed phenotypes. We therefore specifically inactivated GR, by stereotactic injection of AAV2 expressing the Cre recombinase and the GFP in GRloxP/loxP mice. Control animals were injecting in parallel with an AAV2 expressing only the GFP. We performed locomotor sensitization to cocaine in mutant and control animals. We observed a marked sensitization but no differences between genotypes.