Title

31. Neurotoxicity Gene Expression Following Adolescent Amphetamine and Methylphenidate Exposure

Faculty Mentor(s)

Ryan A. Shanks, Steven A. Lloyd

Campus

Dahlonega

Proposal Type

Poster

Subject Area

Biology

Location

Library Technology Center 3rd Floor Common Area

Start Date

24-3-2017 12:45 PM

End Date

24-3-2017 2:00 PM

Description/Abstract

There is a well-documented increase in the use, misuse, and diversion of prescription stimulants used to treat ADHD, especially for adolescents. Considering the sensitivity of neural development during adolescence, there is a need to investigate the implications of these drug exposures. We previously studied the alteration of dopamine- and neuroplasticity-related gene expressions in the dopaminergic prefrontal cortex (PFC) and striatum (STR) following exposure to clinically relevant doses of amphetamine (Adderall; AMPH) and methylphenidate (Ritalin; MPD). From our findings, we hypothesized that MPD exposure has neurotoxic implications, decreasing gene expression, and AMPH-induced neuroplasticity is coupled with change in neurotoxicity gene expressions. Female and male C57Bl/6J mice were given 1mg/kg of AMPH, MPD, or an equivalent volume of saline during early adolescence (P22-31). After the last injection, the STR and PFC were micro-dissected and the total RNA from each region was isolated. We noted mRNA expression changes of genes using a PCR neurotoxicity-array in several functional domains using quantitative RT-PCR. In both the PFC the STR, drug, drug by sex, and drug by sex by domain differences were noted. With many alterations inducing apoptosis and few inhibiting apoptosis, apoptosis is a candidate for neurotoxic effects in both AMPH and MPD treatments. Overall the genetic expression patterns suggest a greater effect in the male PFC. The drug-induced effects extrapolated provide valuable insight into the susceptibility to drug-induced neurotoxicity during this key developmental window of early adolescence. Such long-term susceptibility to psychostimulant-induced neurotoxicity has many implications to include neuroplasticity, behavioral regulation, and clinical outcomes.

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Mar 24th, 12:45 PM Mar 24th, 2:00 PM

31. Neurotoxicity Gene Expression Following Adolescent Amphetamine and Methylphenidate Exposure

Library Technology Center 3rd Floor Common Area

There is a well-documented increase in the use, misuse, and diversion of prescription stimulants used to treat ADHD, especially for adolescents. Considering the sensitivity of neural development during adolescence, there is a need to investigate the implications of these drug exposures. We previously studied the alteration of dopamine- and neuroplasticity-related gene expressions in the dopaminergic prefrontal cortex (PFC) and striatum (STR) following exposure to clinically relevant doses of amphetamine (Adderall; AMPH) and methylphenidate (Ritalin; MPD). From our findings, we hypothesized that MPD exposure has neurotoxic implications, decreasing gene expression, and AMPH-induced neuroplasticity is coupled with change in neurotoxicity gene expressions. Female and male C57Bl/6J mice were given 1mg/kg of AMPH, MPD, or an equivalent volume of saline during early adolescence (P22-31). After the last injection, the STR and PFC were micro-dissected and the total RNA from each region was isolated. We noted mRNA expression changes of genes using a PCR neurotoxicity-array in several functional domains using quantitative RT-PCR. In both the PFC the STR, drug, drug by sex, and drug by sex by domain differences were noted. With many alterations inducing apoptosis and few inhibiting apoptosis, apoptosis is a candidate for neurotoxic effects in both AMPH and MPD treatments. Overall the genetic expression patterns suggest a greater effect in the male PFC. The drug-induced effects extrapolated provide valuable insight into the susceptibility to drug-induced neurotoxicity during this key developmental window of early adolescence. Such long-term susceptibility to psychostimulant-induced neurotoxicity has many implications to include neuroplasticity, behavioral regulation, and clinical outcomes.