RATIONALE: The role of positive vs negative ethanol reinforcement in ethanol intake of Sardinian alcohol-preferring (sP) rats is unclear. OBJECTIVES: To test the hypothesis that spontaneous ethanol self-administration of sP rats was sensitive to the opioid receptor antagonist naltrexone, whereas withdrawal-induced, but not spontaneous, ethanol self-administration would be sensitive to corticotropin-releasing factor(1) (CRF(1)) antagonists, implicating differential roles for positive and negative reinforcement, respectively. METHODS: Male sP rats operantly (FR1, 30 min/day) self-administered ethanol (10% v/v) until responding stabilized. One group (n=11) was made ethanol dependent through intermittent ethanol vapor exposure. Both nondependent (n = 10) and dependent rats received the CRF(1) antagonist LWH-63 (5, 10, and 20 mg/kg, s.c.). Separate nondependent sP rats (n = 10) received the opioid antagonist naltrexone (16, 50, 150, and 450 microg/kg, s.c.). Finally, CRF(1) antagonists (MJL-1-109-2, LWH-63, and R121919) were studied for their actions on home-cage ethanol drinking in nondependent sP rats (n = 6-8/group) under continuous, limited-access, or stressed conditions. RESULTS: Naltrexone potently reduced ethanol self-administration in nondependent sP rats. LWH-63 reduced heightened ethanol self-administration of vapor-sensitive, dependent sP rats. CRF(1) antagonists did not reduce ethanol intake in nondependent sP rats. R121919 (10 mg/kg, s.c.) retained antistress activity in sP rats, blunting novelty stress-induced suppression of ethanol intake. CONCLUSIONS: Spontaneous ethanol self-administration of sP rats was opioid dependent with CRF(1) receptors implicated in withdrawal-induced drinking. Opioid and CRF(1) receptors play different roles in ethanol reinforcement and perhaps the ethanol addiction cycle. Such distinctions may apply to subtypes of alcoholic patients who differ in their motivation to drink and ultimately treatment response.
RATIONALE: The role of positive vs negative ethanol reinforcement in ethanol intake of Sardinian alcohol-preferring (sP) rats is unclear. OBJECTIVES: To test the hypothesis that spontaneous ethanol self-administration of sPrats was sensitive to the opioid receptor antagonist naltrexone, whereas withdrawal-induced, but not spontaneous, ethanol self-administration would be sensitive to corticotropin-releasing factor(1) (CRF(1)) antagonists, implicating differential roles for positive and negative reinforcement, respectively. METHODS: Male sPrats operantly (FR1, 30 min/day) self-administered ethanol (10% v/v) until responding stabilized. One group (n=11) was made ethanol dependent through intermittent ethanol vapor exposure. Both nondependent (n = 10) and dependent rats received the CRF(1) antagonist LWH-63 (5, 10, and 20 mg/kg, s.c.). Separate nondependent sPrats (n = 10) received the opioid antagonist naltrexone (16, 50, 150, and 450 microg/kg, s.c.). Finally, CRF(1) antagonists (MJL-1-109-2, LWH-63, and R121919) were studied for their actions on home-cage ethanol drinking in nondependent sPrats (n = 6-8/group) under continuous, limited-access, or stressed conditions. RESULTS:Naltrexone potently reduced ethanol self-administration in nondependent sPrats. LWH-63 reduced heightened ethanol self-administration of vapor-sensitive, dependent sPrats. CRF(1) antagonists did not reduce ethanol intake in nondependent sPrats. R121919 (10 mg/kg, s.c.) retained antistress activity in sPrats, blunting novelty stress-induced suppression of ethanol intake. CONCLUSIONS:Spontaneous ethanol self-administration of sPrats was opioid dependent with CRF(1) receptors implicated in withdrawal-induced drinking. Opioid and CRF(1) receptors play different roles in ethanol reinforcement and perhaps the ethanol addiction cycle. Such distinctions may apply to subtypes of alcoholicpatients who differ in their motivation to drink and ultimately treatment response.
Authors: Heike E Künzel; Astrid W Zobel; Thomas Nickel; Nibal Ackl; Manfred Uhr; Annette Sonntag; Marcus Ising; Florian Holsboer Journal: J Psychiatr Res Date: 2003 Nov-Dec Impact factor: 4.791
Authors: Thomas N Greenwell; Cindy K Funk; Pietro Cottone; Heather N Richardson; Scott A Chen; Kenner C Rice; Eric P Zorrilla; George F Koob Journal: Addict Biol Date: 2009-04 Impact factor: 4.280
Authors: Richard L Bell; Helen J K Sable; Giancarlo Colombo; Petri Hyytia; Zachary A Rodd; Lawrence Lumeng Journal: Pharmacol Biochem Behav Date: 2012-07-25 Impact factor: 3.533
Authors: Lynda Sharrett-Field; Tracy R Butler; Jennifer N Berry; Anna R Reynolds; Mark A Prendergast Journal: Alcohol Clin Exp Res Date: 2013-03-25 Impact factor: 3.455