EPIGENETIC TRANSMISSION OF NICOTINIC EFFECTS WITHIN THE NEONATAL QUINPIROLE RODENT MODEL OF SCHIZOPHRENIA

Schizophrenia is a neurological disorder found in approximately 1% of the population. It is estimated that as many as 88% of individuals diagnosed which schizophrenia smoke tobacco, a rate which is greatly increased compared to the general population. While increased use of nicotine-containing products such as cigarettes may be detrimental to the long-term health of individuals with schizophrenia, it has been hypothesized that nicotine use is a form of self-medication for these individuals who suffer from serious neurological and psychological symptoms such as hallucinations, delusions, anhedonia, and cognitive impairments. Understanding the biomolecular mechanisms which result in a higher propensity for smoking may lead to an overall better understanding of the disease and new treatment options. This study investigated the effects of nicotine in an epigenetic transmission model of schizophrenia. Rats were treated neonatally with the dopamine D2 agonist quinpirole or saline from P1 to P21 and then raised into adulthood. This paradigm has been previously shown to produce rats with symptoms similar to schizophrenia, including an enhanced response to nicotine. These neonatally treated rats were then bred to produce pups which were not neonatally treated to investigate whether schizophrenia-like symptoms would be transmitted to the untreated offspring of the quinpirole treated parents in the context of nicotine administration, similar to that of their parents. To examine the effects of nicotine, the rats that were the offspring of animals that were neonatally treated quinpirole were behaviorally tested on either a behavioral sensitization or conditioned place preference (CPP) paradigm, and animals received either nicotine or saline. Following behavioral testing, brain tissue was collected, and an ELISA for brain-derived neurotrophic factor (BDNF) was performed. Results revealed that these offspring demonstrated a heightened behavioral response to nicotine as well as increased expression of BDNF following nicotine administration if at least one parent rat was neonatally treated with quinpirole. This indicates that there may be epigenetic information passed from parents neonatally treated with quinpirole to the offspring