Corticostriatal CDK5/p35 expression is differentially affected following cocaine place conditioning in adult rats depending on their exposure to prenatal stress

ANTONELLI, MARTA C.; PALLARÉS, MARÍA EUGENIA; SANABRIA, VALERIA; PASTOR, VERONICA

Virtual

Simposio; 7th International symposium on resilience research; 2021

Cocaine is one of the most abused substances globally and has a high potential of generating addictive-like behaviors. One of the risk factors in the development of drug-seeking behaviors during adulthood is prenatal stress (PS), which promotes changes in the development of the nervous system. Despite its relevance, molecular mechanisms underlying cocaine vulnerability in PS models have been poorly explored. Growing evidence suggest that cocaine behavioral effects are regulated by CDK5 and its activator p35, although this pathway has not been explored in PS rats. To analyze if this pathway is affected by PS, we performed a conditioning place preference (CPP) assay to assess cocaine-seeking behavior in PS rats and then studied Cyclin dependant kinase 5 (CDK5) & p35 protein expression in the corticostriatal circuit by Western Blot. We found an increased cocaine-seeking and a lower initial locomotor response to cocaine in PS rats. Western blot results showed a CDK5 increase in the striatum of control cocaine-treated rats which was not found in PS rats, in line with a previously suggested protective role of striatal CDK5 against cocaine behavioral effects. Conversely, p35, one of CDK5 main activators, was increased by cocaine CPP in the nucleus Accumbens of PS rats. No changes were found for CDK5/p35 in the medial prefrontal cortex. These results suggest that cocaine differentially affects the CDK5/p35 expression in the corticostriatal circuit of PS and control rats, pointing out this molecular pathway as a potential new target for cocaine-aimed therapies for individuals at risk.