Does Adolescent Exposure to Methylphenidate Elicits Changes in ΔFosB expression? A Possible Underlying Mechanism of Cross-Sensitization

Abstract

Methylphenidate (MPD), a psychostimulant, blocks the dopamine (DA) transporter, leading to increased amounts of extracellular DA, especially in the prefronal cortex (PFC) and striatum (STR). Previous studies in our lab suggest that adolescent exposure to MPD will result in drug and sex-dependent effects on cross-sensitization in adulthood. Cross-sensitization is a phenomenon in which exposure to one drug leads to hyper-responsiveness to another drug, which is a hallmark of addiction. This study examines genetic alterations after adolescent MPD exposure in an effort to elucidate the underlying mechanisms of cross-sensitization. ΔFosB is a transcription factor associated with long-term neural plastic changes. It is expressed in response to psychostimulants and has many key downstream targets. Given the previously noted behavioral effects, we expect to find increases in ∆FosB levels in the PFC and STR following adolescent MPD exposure in a C57Bl6/J model. To address sexual dimorphism in previous behavioral data, we also expect to find higher expression levels in females compared to males. The PFC and STR will be microdissected, processed for RNAisolation, and analyzed using RT-PCR with ∆FosB specific primers. Increased ∆FosB expression would suggest a link between MPD exposure, genetic alterations, and long-lasting behavioral changes.