Role of perineuronal nets in the frontal cortex in compulsive rats selected by schedule-induced polydipsia

Compulsive behavior, observed in several neuropsychopathological disorders, reflects a deficiency in inhibitory control. This inability to cease actions is associated with abnormal activation and plasticity in the Frontal Cortex (FC). Perineuronal nets (PNNs), which enwrap the cell-body and proximal dendrites of neurons, have been proposed as a candidate mechanism for modulating neuroplasticity. We investigated the changes in activation (cFos expression) and in plasticity (PNN expression) in different regions of the FC through immunolabeling and confocal microscopy in rats selected as high or low compulsive drinking (HD, LD) on Schedule-Induced Polydipsia (SIP). SIP exposure induced plasticity changes in the brains of HD compared to LD animals. HD rats presented an increased number of PNNs in Infralimbic Cortex and increased intensity and integrity of PNNs in Orbitofrontal Cortex. There were no differences between HD and LD either in the number, intensity, and integrity of PNNs in the Prelimbic Cortex or activity in none of the regions evaluated. These results showed neuroplasticity alterations, which may underlie the behavioral deficits present in the compulsive phenotype, suggesting that the PNN upregulation in Infralimbic Cortex may be linked with the development of repetitive behaviors, and the higher intensity and integrity of PNNs in Orbitofrontal Cortex may be related to the expression and maintenance of them.Work supported by: PID2022-139286NB-I00 funded by MCIN/AEI/10.13039/ 501100011033; PND-2022l024 funded by MISAN; SUBV23/00027 funded by MIC; PGC2018-095980-B-I00 funded by MCIN/AEI/10.13039/ 501100011033 and by “ERDF A way of making Europe”; UJI-B2020-1 funded by Plan de Promoción de la Investigación.