Effects of Adolescent Nicotine Exposure on Acute and Chronic Ethanol Consumption in a Heritable Model of Psychosis

Abstract

Schizophrenia (SZ) is characterized by sensorimotor gating deficits, disordered thought processes, and hallucinations. Individuals diagnosed with SZ often exhibit comorbid substance abuse, particularly nicotine and alcohol (EtOH) use disorder. Our laboratory has established a novel heritable model of schizophrenia administering neonatal quinpirole (NQ), a dopamine (DA) D2-like receptor agonist (1 mg/kg), which results in permanent increases of DAD2 receptor sensitivity throughout the animal\u27s lifetime. We have shown offspring of male-female pairs of NQ-treated rats (QQ) demonstrate heritability of increased DAD2 sensitivity, consistent with clinical data. In the current study, male and female Sprague-Dawley rats that were postnatal day (PND) 28-48 days of age were given a two-bottle choice (2BC) test with water or water with 10% ethanol for 24 hours daily. On each day, animals were administered intraperitoneal (IP) injections of nicotine (0.6 mg/kg base). We assessed drinking of EtOH at the 3- and 6-h post-injection time points. Chronic drinking was assessed based on 24-h drinking measurements. Following 21-days of EtOH/nicotine exposure, nicotine injections and EtOH ceased from PND 49-62. During this period, locomotor activity was recorded as a measurement of withdrawal over 4 days of testing. In adulthood, a 2BC test was also conducted from PND 63-76. Results revealed adolescent nicotine exposure enhanced EtOH drinking in QQ animals. During withdrawal, QQ females given nicotine demonstrated enhanced locomotor activity and showed lack of habituation compared to other groups. Significant enhancement of acute EtOH following nicotine administration was also observed at the 3- and 6-h marks for the quinpirole (QQ) rats in adolescence compared to control (SS) rats at PND 63. Prefrontal cortex oxidative stress is being assessed using a TBARS assay (data will be presented). Findings suggest that adolescent exposure to nicotine and ethanol can have long-lasting effects on EtOH consumption in a heritable model of psychosis