Examining the Long-Term Effects of Early Adolescent Meth and/or Nicotine Exposure on Behavior, Cognition, Corticosterone, and the Dopamine Transporter System in the Brain.

Methamphetamine (meth) is a highly addictive and powerful psychomotor stimulant that affects the central nervous system. Many adolescents who use meth also smoke cigarettes. However, the interactive effects of meth and nicotine on the adolescent brain remain unknown. Thus we were interested in examining the long-term effects of early adolescent meth and/or nicotine use on behavior, cognition, serum corticosterone (CORT), and the dopamine transporter system in the brain. It was hypothesized that early adolescent meth exposure would impair behavior and cognition, increase meth-induced conditioned place preference, decrease serum CORT levels, and that the co-administration of meth and nicotine would mitigate meth-induced behavioral changes and the decreases in CORT.

Male mice were administered meth, nicotine, meth and nicotine, or saline over a 2-day period during early adolescence. Mice were tested in the open field test (test of locomotor activity and anxiety-like behavior), the novel object recognition test (test of object memory), the Porsolt forced swim test (test of depression-like behavior), the Morris water maze test (test of spatial memory), and meth-induced conditioned place preference (test of meth craving) later in adolescence. Serum was collected from mice following conditioned place preference testing in order to analyze serum corticosterone levels using an enzyme-linked immunosorbent assay (ELISA). Currently dopamine transporter immunohistochemistry is being performed in various brain regions. Results showed that the mice administered meth or nicotine spent a greater time in the center of the open field test, which indicates increased risk taking behavior, or decreased anxiety, compared to the saline and meth/nicotine mice. Meth-induced CPP was established for all mice, but there were no significant group differences. There was a trend for decreased CORT in meth-exposed mice compared to saline-exposed mice, but there were no other group differences in the serum CORT levels. 

The results of this study demonstrate that meth and nicotine exposure during early adolescence can increase risk-taking behavior, while co-administration of meth/nicotine returns these behavioral changes to control levels. The result of no group differences in meth-induced CPP demonstrates that prior meth exposure does not enhance meth-seeking behavior later in adolescence. Since CORT mediates anxiety and risk-taking behavior, finding reduced CORT in the meth-exposed mice could account for the increased time spent in the center of the open field.

This work was performed by Sewanee undergraduate students Jordan Buck '15 and Alysse Schultheis '16 and by Dr. Jessica Siegel. Current work is ongoing in the lab to perform dopamine transporter immunohistochemistry. The findings from this study were presented at the Society for Neuroscience (SfN) conference in November 2014.