RATIONALE: 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.
RATIONALE: 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.
Authors: Zachary A Rodd; Richard L Bell; Roberto I Melendez; Kelly A Kuc; Lawrence Lumeng; Ting-Kai Li; James M Murphy; William J McBride Journal: Alcohol Clin Exp Res Date: 2004-08 Impact factor: 3.455
Authors: Zachary A Rodd; Roberto I Melendez; Richard L Bell; Kelly A Kuc; Ying Zhang; James M Murphy; William J McBride Journal: J Neurosci Date: 2004-02-04 Impact factor: 6.167
Authors: Volodymyr I Pidoplichko; Jun Noguchi; Oluwasanmi O Areola; Yong Liang; Jayms Peterson; Tianxiang Zhang; John A Dani Journal: Learn Mem Date: 2004 Jan-Feb Impact factor: 2.460
Authors: Olga Karatayev; Olga Lukatskaya; Sang-Ho Moon; Wei-Ran Guo; Dan Chen; Diane Algava; Susan Abedi; Sarah F Leibowitz Journal: Alcohol Date: 2015-04-11 Impact factor: 2.405
Authors: R L Bell; S Hauser; Z A Rodd; T Liang; Y Sari; J McClintick; S Rahman; E A Engleman Journal: Int Rev Neurobiol Date: 2016-03-21 Impact factor: 3.230
Authors: Robert A Waeiss; Christopher P Knight; Gustavo B Carvajal; Richard L Bell; Eric A Engleman; William J McBride; Sheketha R Hauser; Zachary A Rodd Journal: Behav Brain Res Date: 2019-08-29 Impact factor: 3.332
Authors: Robert A Waeiss; Christopher P Knight; Sheketha R Hauser; Lauren A Pratt; William J McBride; Zachary A Rodd Journal: Psychopharmacology (Berl) Date: 2019-02-13 Impact factor: 4.530
Authors: Kyu Y O'Rourke; Jillienne C Touchette; Elizabeth C Hartell; Elizabeth J Bade; Anna M Lee Journal: Neuropharmacology Date: 2016-06-21 Impact factor: 5.250
Authors: Gerald A Deehan; Sheketha R Hauser; R Aaron Waeiss; Christopher P Knight; Jamie E Toalston; William A Truitt; William J McBride; Zachary A Rodd Journal: Psychopharmacology (Berl) Date: 2015-08-26 Impact factor: 4.530
Authors: Gerald A Deehan; Sheketha R Hauser; Bruk Getachew; R Aaron Waeiss; Eric A Engleman; Christopher P Knight; William J McBride; William A Truitt; Richard L Bell; Zachary A Rodd Journal: Psychopharmacology (Berl) Date: 2018-07-24 Impact factor: 4.530