Discipline: Biological Sciences
Subcategory: Biochemistry (not Cell and Molecular Biology and Genetics)
Jonathan Salas - Binghamton University
Co-Author(s): Matthew C Wend, Binghamton University, Binghamton, NY
Although prenatal alcohol exposure (PAE) induced mental disorders are preventable, 1:10 pregnant women report consuming at least one alcoholic beverage in the past 30 days and 1:33 report binge drinking. With over 50% of PAE adults being diagnosed with substance abuse disorder, mechanistic studies of PAE-induced neuroplasticity are of extreme importance. Thus, this procedure seeks to answer if we can establish a rodent model to investigate neuroplasticity as a consequence of prenatal alcohol exposure. I hypothesize that using the most currently accepted model of drug-taking, intravenous self-administration (IVSA), I can demonstrate a significant difference in cocaine taking between PAE and control adolescent rats. These rodent models can then be used for glutamatergic synaptic studies for the prevention and treatment of PAE-induced mental disorders. In order to produce PAE offspring, pregnant females were subjected to twice daily intragastric ethanol administration (3g/kg) from gestational (G) day 17-20 or water for the controls (PCE). Offspring were then weaned on postnatal (P) day 23 and subjected to jugular vein catheterization surgery on P28. The surgery was performed under isoflurane anesthesia and was followed by 3 days of ketoprofen (5mg/kg s.c.) and 7 days of gentamicin (mg/kg i.v.). To maintain catheter patency, catheters were flushed with heparinized (10 U per mL, i.v.) saline up to twice daily until the end of the IVSA procedure. Once the animals have healed from the surgery, the adolescent PAE offspring received a 12-hour overnight behavior shaping session of cocaine IVSA in an operant conditioning chamber. After a one-night break, they received 5-days of 2-hour IVSA cocaine training during P38-P42. On P43, a within-subject cocaine IVSA dose response (DR) test was performed followed by a propofol (10mg/mL i.v.) test to confirm catheter patency. A dose-response evaluation to four dosages of cocaine was then evaluated on 8 litters worth of animals for each condition. We present the results of the first 10 minutes of the 0.1mg/kg condition. Our preliminary data showed that both animals developed a preference for the active lever, even so PAE animals self-infused more cocaine than their PCE counterparts. Thus we conclude that this model successfully demonstrated increased cocaine taking in adolescent rats as a result of PAE, suggesting an increased addictive liability to illegal drugs. This animal model will subsequently be used for circuit-specific glutamatergic synaptic plasticity studies in conjunction with whole-cell patch clamp and optogenetics. We hope this will aid in identification of novel and precise targets to prevent and treat PAE-induced mental disorders such as substance abuse.
Funder Acknowledgement(s): Yaoying Ma
Faculty Advisor: Yaoying Ma, May@binghamton.edu
Role: My role in this was as head surgeon and behavioral trainer. I performed the majority of the surgeries, associated post-operative care, and behavioral training on the PAE offspring. ]