RATIONALE: Manipulation of the stress neuropeptide corticotropin-releasing factor (CRF), specifically central antagonism of the type 1 receptors (CRF-R1), effectively reduces alcoholic-like ethanol drinking in rodents. Escalated consumption is largely controlled by neurocircuitry that is important for reward and affect, such as the ventral tegmental area (VTA) and the dorsal raphé nucleus (DRN). OBJECTIVE: The current studies investigated the role of CRF-R1 within the VTA and DRN and their relation to escalated ethanol drinking in two species. An additional goal was to explore whether high alcohol-drinking individuals would be more affected by CRF-R1 antagonism than low alcohol-drinking individuals. METHODS: With a two-bottle choice drinking procedure, adult male C57BL/6J mice and Long-Evans rats were given 24-h access to 20 % ethanol and water on an intermittent schedule. Rats and mice were implanted with cannulae targeting the VTA or DRN. Doses of the CRF-R1 antagonist CP-154,526 (butyl-[2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine)) were microinfused to modulate drinking of ethanol and water over the course of 24 h. RESULTS: In both mice and rats, intra-VTA CP-154,526 selectively decreased ethanol intake, while identical doses (0.3 and 0.6 μg) infused intra-DRN reduced both ethanol and water drinking. Long-Evans rats displayed a range of individual differences for ethanol preference, and CP-154,526 suppressed ethanol drinking in the high-preferring animals regardless of brain site manipulation. CONCLUSIONS: The current findings confirm previous studies that blockade of CRF-R1 efficaciously reduces escalated drinking while also suggesting that the effects of intermittent access on alcohol consumption may require CRF interaction with dopamine in the VTA.
RATIONALE: Manipulation of the stress neuropeptide corticotropin-releasing factor (CRF), specifically central antagonism of the type 1 receptors (CRF-R1), effectively reduces alcoholic-like ethanol drinking in rodents. Escalated consumption is largely controlled by neurocircuitry that is important for reward and affect, such as the ventral tegmental area (VTA) and the dorsal raphé nucleus (DRN). OBJECTIVE: The current studies investigated the role of CRF-R1 within the VTA and DRN and their relation to escalated ethanol drinking in two species. An additional goal was to explore whether high alcohol-drinking individuals would be more affected by CRF-R1 antagonism than low alcohol-drinking individuals. METHODS: With a two-bottle choice drinking procedure, adult male C57BL/6J mice and Long-Evans rats were given 24-h access to 20 % ethanol and water on an intermittent schedule. Rats and mice were implanted with cannulae targeting the VTA or DRN. Doses of the CRF-R1 antagonist CP-154,526 (butyl-[2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine)) were microinfused to modulate drinking of ethanol and water over the course of 24 h. RESULTS: In both mice and rats, intra-VTA CP-154,526 selectively decreased ethanol intake, while identical doses (0.3 and 0.6 μg) infused intra-DRN reduced both ethanol and water drinking. Long-Evans rats displayed a range of individual differences for ethanol preference, and CP-154,526 suppressed ethanol drinking in the high-preferring animals regardless of brain site manipulation. CONCLUSIONS: The current findings confirm previous studies that blockade of CRF-R1 efficaciously reduces escalated drinking while also suggesting that the effects of intermittent access on alcohol consumption may require CRF interaction with dopamine in the VTA.
Authors: Emily G Lowery-Gionta; Montserrat Navarro; Chia Li; Kristen E Pleil; Jennifer A Rinker; Benjamin R Cox; Gretchen M Sprow; Thomas L Kash; Todd E Thiele Journal: J Neurosci Date: 2012-03-07 Impact factor: 6.167
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Authors: Melissa A Herman; Marsida Kallupi; George Luu; Christopher S Oleata; Markus Heilig; George F Koob; Roberto Ciccocioppo; Marisa Roberto Journal: Neuropharmacology Date: 2012-12-04 Impact factor: 5.250
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