Vendor differences in alcohol consumption and the contribution of dopamine receptors to Pavlovian-conditioned alcohol-seeking in Long-Evans rats
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Drug-associated environmental stimuli elicit craving in humans and drug-seeking in animals.
We tested the hypothesis that Pavlovian-conditioned alcohol-seeking is mediated by dopamine, using rats from two vendors.
Male, Long–Evans rats (220–240 g) from Charles River (St-Constant, QC, Canada) and Harlan Laboratories (Indianapolis, IN, USA) received 21 sessions of intermittent, 24-h access to ethanol (15 %, v/v) and water in the home-cage. Subsequently, rats were trained to discriminate between one conditioned stimulus (CS+) that was paired with ethanol (0.2 ml per CS+) and a second stimulus (CS−) that was not. Entries into a fluid port where ethanol was delivered were recorded. Next, rats were exposed to a different context where cues and ethanol were withheld. At test, responding to the CS+ and CS− without ethanol was assessed in the second, non-alcohol context. Injections (1 ml/kg; s.c.) of the dopamine D1-receptor antagonist SCH 23390 (0, 3.33, and 10 μg/kg) or dopamine D2-receptor antagonist eticlopride (0, 5, and 10 μg/kg) were administered before test.
Home-cage alcohol consumption was higher in Harlan rats than Charles River rats. At test, saline-treated rats responded more to the alcohol-predictive CS+ than the CS−. While SCH 23390 attenuated CS+ responding in rats from both vendors, eticlopride reduced CS+ responding in Harlan rats only. Subsequently, SCH 23390 but not eticlopride attenuated CS+ responding when the CS+ was again paired with ethanol.
These results indicate important differences in alcohol consumption in Long–Evans rats from different suppliers, and highlight a novel role for dopamine in Pavlovian-conditioned alcohol-seeking.
KeywordsAlcoholism Relapse Reinstatement Craving Dopamine Long–Evans SCH 23390 Eticlopride Context Cues
The National Institute of Alcohol Abuse and Alcoholism (RO1 AA14925; Patricia H. Janak, PI) funded this research. NC is the recipient of a Chercheurs-Boursiers award from Fonds de recherche du Québec - Santé, and a member of the FRQS-funded Center for Studies in Behavioral Neurobiology/Groupe de recherche en neurobiologie comportementale (CSBN/GRNC). The authors would like to thank Dr. Uri Shalev for comments on the manuscript and Atyeh Heidari for assistance in running the experiments.
- Berglind WJ, Case JM, Parker MP, Fuchs RA, See RE (2006) Dopamine D1 or D2 receptor antagonism within the basolateral amygdala differentially alters the acquisition of cocaine-cue associations necessary for cue-induced reinstatement of cocaine-seeking. Neuroscience 137:699–706. doi: 10.1016/j.neuroscience.2005.08.064 PubMedCrossRefGoogle Scholar
- Bossert JM, Poles GC, Wihbey KA, Koya E, Shaham Y (2007) Differential effects of blockade of dopamine D1-family receptors in nucleus accumbens core or shell on reinstatement of heroin-seeking induced by contextual and discrete cues. J Neurosci 27:12655–12663. doi: 10.1523/JNEUROSCI.3926-07.2007 PubMedCentralPubMedCrossRefGoogle Scholar
- Ciccocioppo R, Sanna PP, Weiss F (2001) Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci U S A 98:1976–1981. doi: 10.1073/pnas.98.4.1976 PubMedCentralPubMedCrossRefGoogle Scholar
- Fuchs RA, Evans KA, Ledford CC, Parker MP, Case JM, Mehta RH, See RE (2004) The role of the dorsomedial prefrontal cortex, basolateral amygdala, and dorsal hippocampus in contextual reinstatement of cocaine-seeking in rats. Neuropsychopharmacology 30:296–309. doi: 10.1038/sj.npp.1300579 CrossRefGoogle Scholar
- Keppel G (1991) Design and analysis: a researcher’s handbook. Prentice-Hall, New JerseyGoogle Scholar
- McCusker CG, Brown K (1989) Alcohol-predictive cues enhance tolerance to and precipitate “craving” for alcohol in social drinkers. J Stud Alcohol 51:494–499Google Scholar
- Roman E, Gustafsson L, Hyyti P, Nylander I (2005) Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats. Alcohol Clin Exp Res 29:591–601. doi: 10.1097/01.ALC.0000158933.70242.FC PubMedCrossRefGoogle Scholar
- Simms JA, Steensland P, Medina B, Abernathy KE, Chandler LJ, Wise R, Bartlett SE (2008) Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats. Alcohol Clin Exp Res 32:1816–1823. doi: 10.1111/j.1530-0277.2008.00753.x PubMedCentralPubMedCrossRefGoogle Scholar