Truitt, William A.Hauser, Sheketha R.Deehan, Gerald A.Toalston, Jamie E.Wilden, Jessica A.Bell, Richard L.McBride, William J.Rodd, Zachary A.2016-05-312016-05-312015-02Truitt, W. A., Hauser, S. R., Deehan, G. A., Toalston, J. E., Wilden, J. A., Bell, R. L., … Rodd, Z. A. (2015). Ethanol and nicotine interaction within the posterior ventral tegmental area in male and female alcohol-preferring rats: evidence of synergy and differential gene activation in the nucleus accumbens shell. Psychopharmacology, 232(3), 639–649. http://doi.org/10.1007/s00213-014-3702-3https://hdl.handle.net/1805/9696RATIONALE: Ethanol and nicotine are frequently co-abused. The biological basis for the high co-morbidity rate is not known. Alcohol-preferring (P) rats will self-administer EtOH or nicotine directly into the posterior ventral tegmental area (pVTA). OBJECTIVE: The current experiments examined whether sub-threshold concentrations of EtOH and nicotine would support the development of self-administration behaviors if the drugs were combined. METHODS: Rats were implanted with a guide cannula aimed at the pVTA. Rats were randomly assigned to groups that self-administered sub-threshold concentrations of EtOH (50 mg%) or nicotine (1 μM) or combinations of ethanol (25 or 50 mg%) and nicotine (0.5 or 1.0 μM). Alterations in gene expression downstream projections areas (nucleus accumbens shell, AcbSh) were assessed following a single, acute exposure to EtOH (50 mg%), nicotine (1 μM), or ethanol and nicotine (50 mg% + 1 μM) directly into the pVTA. RESULTS: The results indicated that P rats would co-administer EtOH and nicotine directly into the pVTA at concentrations that did not support individual self-administration. EtOH and nicotine directly administered into the pVTA resulted in alterations in gene expression in the AcbSh (50.8-fold increase in brain-derived neurotrophic factor (BDNF), 2.4-fold decrease in glial cell line-derived neurotrophic factor (GDNF), 10.3-fold increase in vesicular glutamate transporter 1 (Vglut1)) that were not observed following microinjections of equivalent concentrations/doses of ethanol or nicotine. CONCLUSION: The data indicate that ethanol and nicotine act synergistically to produce reinforcement and alter gene expression within the mesolimbic dopamine system. The high rate of co-morbidity of alcoholism and nicotine dependence could be the result of the interactions of EtOH and nicotine within the mesolimbic dopamine system.Brain-Derived Neurotrophic FactorDrug SynergismGlial Cell Line-Derived Neurotrophic FactorNicotineTobacco Use DisorderAlcoholismArticle