Increasing glutamatergic transmission in the rat infralimbic cortex evokes antidepressant-like effects

Póster presentada en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis CatalansRecent basic and clinical studies suggest a main role of the glutamate system in the pathophysiology of depression. However, the precise mechanism by which glutamate modulates mood and emotions remains unknown. Neuroimaging studies have reported functional and metabolic alterations in the medial prefrontal cortex (mPFC) of depressed patients -particularly in its ventral regions- and these abnormalities are hypothesized to result from glial dysfunction, as shown in rodent and human studies. The current studies were conducted to determine the behavioral and neurochemical effects of glutamate modulation in the different subregions of the rat mPFC. We performed local infusions of veratridine (0.5 µl, 100 µM), a depolarizing agent, in the infralimbic cortex (IL) and the prelimbic cortex (PL) and assessed behavior in the forced swimming test (FST). We found that veratridine infusion into IL, but not in PL, produced rapid antidepressant effects. We observed similar antidepressant effects after the infusion of dihydrokainic acid (DHK) (0.5 µl, 10 mM) in IL. This agent is a GLT1 selective inhibitor that prevents astrocytic glutamate uptake. In addition, preliminary data obtained in the novelty suppressed feeding test (NSFT) also suggests antidepressant effects of DHK application into IL. This effect appears to be mediated by an increase of glutamatergic neurotransmission in IL, as assessed by in vivo microdialysis studies. Interestingly, we also found increased serotonin levels, which may be accounted for by reciprocal connectivity between the IL and the raphe nuclei. Overall, these findings suggest antidepressantlike effects after enhancing glutamatergic neurotransmission in ILSpanish Ministry of Economy and Competitiveness, SAF2012-35183. Co-financed by FEDER; Spanish Ministry of Economy and Competitiveness, BES-2013-063241Peer Reviewe