Inhibition of neuronal activity in the prefrontal cortex after systemic administration of fluoxetine during the execution of an operant conditioning task

A. E. PEREYRA ; C. MININNI; B. S. ZANUTTO

Chicago Estados Unidos

Congreso; Neuroscience 2019; 2019

Sociedad de Neurociencias

AbstractThe prefrontal cortex (PFC) is a main brain region controlling high-level executive functions and goal-directed behaviors. Several neuropsychiatric disorders are related to the deficits in cognitive and emotional processes subserved by PFC. Serotonergic system plays an important role in regulating prefrontal function. It is also involved in depressive disorders, and fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has been a successful antidepressant drug. Although it is well known the effect of fluoxetine on the concentrations of monoamines in the cortex, such as 5-HT, dopamine and noradrenaline, and in other regions related to motivated behaviors, its effect on the activity of the PFC neurons in vivo is not well understood, especially during the execution of a behavioral conditioning task. In this study we performed extracellular recordings of PFC neurons of head-fixed Long Evans rats, during the execution of an operant conditioning task. Rats had to make a lick action after an auditory cue, in order to obtain a drop of water as a reward. Recordings started after behavioral performance was stable and above 80% of correct responses. After 10 sessions of control recordings, fluoxetine was administered on a daily basis (10 mg / kg / day, oral dose) and another 10 sessions were performed. We observed a progressive reduction in the PFC mean firing rate (FR) along sessions after fluoxetine treatment onset, and an increment in mean FR occurs during the consumption for control and fluoxetine recordings. Interestingly, a reduction in FR occurs immediately before cue onset during fluoxetine sessions, which is absent in control recordings. Moreover, the mean FR and the mean correlation between pairs of neurons during consumption?s time were significantly lower for fluoxetine recordings. Our results are consistent with an inhibitory effect of chronic administration of fluoxetine on the pyramidal neurons of the PFC due to a higher excitability of GABAergic interneurons, and contribute to the understanding of the effect of SSRIs on neuronal activity in PFC during the execution of a cognitive task.