CBD treatment following early life seizures alters orbitofrontal-striatal signaling during adulthood

[Display omitted] •While OCD is a co-morbidity of epilepsy, the pathophysiological basis of the disease is not known.•Early-life seizures (ELS) in rats was not found to result in OCD-like behaviors.•ELS causes changes in the theta-slow gamma comodulation in a state-, site- and sex-dependent manner.•CBD alters theta-slow gamma comodulation in a state-, site- and sex-related manner. Obsessive compulsive disorder (OCD) is a comorbid condition of epilepsy and often adds to the burden of epilepsy. Both OCD and epilepsy are disorders of hyperexcitable circuits. Fronto-striatal circuit dysfunction is implicated in OCD. Prior work in our laboratory has shown that in rat pups following a series of flurothyl-induced early life seizures (ELS) exhibit frontal-lobe dysfunction along with alterations in electrographic temporal coordination between the orbitofrontal cortex (OFC) and dorsomedial striatum (DMS), circuits implicated in OCD. Here, we studied the effects of ELS in male and female rat pups on OCD-like behaviors as adults using the marble burying test (MBT). Because cannabidiol (CBD) is an effective antiseizure medication and has shown efficacy in the treatment of individuals with OCD, we also randomized rats to CBD or vehicle treatment following ELS to determine if CBD had any effect on OCD-like behaviors. While the flurothyl model of ELS did not induce OCD-like behaviors, as measured in the MBT, ELS did alter neural signaling in structures implicated in OCD and CBD had sex-dependent effects of temporal coordination in a way which suggests it may have a beneficial effect on epilepsy-related OCD.