BACKGROUND: Identification of the brain regions involved in ethanol administration is important for understanding the neurobiology of ethanol addiction. Animal studies with different brain mapping techniques found that voluntary ethanol self-administration leads to changes in activity of specific brain regions in patterns that only partially overlap with patterns of brain regions affected by involuntary (i.e., experimenter-administered) ethanol administration. As an extension of studies mapping changes in neural activity after voluntary ethanol drinking, this study analyzed expression of the inducible transcription factor c-Fos after ethanol consumption in an operant procedure. METHODS: AA (Alko alcohol) rats were trained to operantly respond for water, 0.2% saccharin, 0.2% saccharin/10% (w/v) ethanol, or 10% ethanol in a 30-min limited-access procedure. Animals were allowed to self-administer solutions for at least 40 ethanol response sessions and were killed 1.5 hr after beginning of the last session. Forty-seven brain regions were immunohistochemically analyzed for c-Fos expression. RESULTS: In this paradigm, ethanol dose-dependently increased c-Fos expression in the Edinger-Westphal nucleus (EW) and decreased expression in the dorsal tenia tecta compared with no-ethanol controls. No effects of saccharin on c-Fos expression were found. CONCLUSIONS: Our results extend previous findings of preferential sensitivity of EW to alcohol in voluntary self-administration procedures to operant responding for ethanol and warrant further investigation of ethanol's effects on the EW. The finding that ethanol attenuated c-Fos expression in the tenia tecta is novel. Taken together, these findings confirm that voluntary ethanol self-administration leads to changes in activity of a limited number of brain regions with previously unexamined roles in ethanol sensitivity and addiction.
BACKGROUND: Identification of the brain regions involved in ethanol administration is important for understanding the neurobiology of ethanol addiction. Animal studies with different brain mapping techniques found that voluntary ethanol self-administration leads to changes in activity of specific brain regions in patterns that only partially overlap with patterns of brain regions affected by involuntary (i.e., experimenter-administered) ethanol administration. As an extension of studies mapping changes in neural activity after voluntary ethanol drinking, this study analyzed expression of the inducible transcription factor c-Fos after ethanol consumption in an operant procedure. METHODS: AA (Alko alcohol) rats were trained to operantly respond for water, 0.2% saccharin, 0.2% saccharin/10% (w/v) ethanol, or 10% ethanol in a 30-min limited-access procedure. Animals were allowed to self-administer solutions for at least 40 ethanol response sessions and were killed 1.5 hr after beginning of the last session. Forty-seven brain regions were immunohistochemically analyzed for c-Fos expression. RESULTS: In this paradigm, ethanol dose-dependently increased c-Fos expression in the Edinger-Westphal nucleus (EW) and decreased expression in the dorsal tenia tecta compared with no-ethanol controls. No effects of saccharin on c-Fos expression were found. CONCLUSIONS: Our results extend previous findings of preferential sensitivity of EW to alcohol in voluntary self-administration procedures to operant responding for ethanol and warrant further investigation of ethanol's effects on the EW. The finding that ethanol attenuated c-Fos expression in the tenia tecta is novel. Taken together, these findings confirm that voluntary ethanol self-administration leads to changes in activity of a limited number of brain regions with previously unexamined roles in ethanol sensitivity and addiction.
Authors: Andrey E Ryabinin; Michael M Tsoory; Tamas Kozicz; Todd E Thiele; Adi Neufeld-Cohen; Alon Chen; Emily G Lowery-Gionta; William J Giardino; Simranjit Kaur Journal: Alcohol Date: 2012-03-22 Impact factor: 2.405
Authors: Tamás Kozicz; Jackson C Bittencourt; Paul J May; Anton Reiner; Paul D R Gamlin; Miklós Palkovits; Anja K E Horn; Claudio A B Toledo; Andrey E Ryabinin Journal: J Comp Neurol Date: 2011-06-01 Impact factor: 3.215
Authors: Olivier George; Chelsea Sanders; John Freiling; Edward Grigoryan; Shayla Vu; Camryn D Allen; Elena Crawford; Chitra D Mandyam; George F Koob Journal: Proc Natl Acad Sci U S A Date: 2012-10-15 Impact factor: 11.205