Differential Effects of Voluntary Ethanol Consumption on Dopamine Output in the Nucleus Accumbens Shell of Roman High- and Low-Avoidance Rats: A Behavioral and Brain Microdialysis Study


The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats.

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Corda, M. , Piras, G. , Piludu, M. and Giorgi, O. (2014) Differential Effects of Voluntary Ethanol Consumption on Dopamine Output in the Nucleus Accumbens Shell of Roman High- and Low-Avoidance Rats: A Behavioral and Brain Microdialysis Study. World Journal of Neuroscience, 4, 279-292. doi: 10.4236/wjns.2014.43031.

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The authors declare no conflicts of interest.


[1] Li, T.K. and Lumeng, L. (1984) Alcohol Preference and Voluntary Alcohol Intakes of Inbred Rat Strains and the National Institutes of Health Heterogeneous Stock of Rats. Alcoholism: Clinical and Experimental Research, 8, 485-486.
[2] Bisaga, A. and Kostowski, W. (1993) Individual Behavioral Differences and Ethanol Consumption in Wistar Rats. Physiology & Behavior, 54, 1125-1131. http://dx.doi.org/10.1016/0031-9384(93)90336-E
[3] Li, T.K., Lumeng, L. and Doolittle, D.P. (1993) Selective Breeding for Alcohol Preference and Associated Responses. Behavior Genetics, 23, 163-170. http://dx.doi.org/10.1007/BF01067421
[4] Sinclair, J.D., Lê, A.D. and Kiianmaa, K. (1989) The AA and ANA Rat Lines, Selected for Differences in Voluntary Alcohol Consumption. Experientia, 45, 798-805. http://dx.doi.org/10.1007/BF01954055
[5] Colombo, G., Agabio, R., Lobina, C., Reali, R., Zocchi, A., Fadda, F. and Gessa, G.L. (1995) Sardinian Alcohol-Preferring Rats: A Genetic Animal Model of Anxiety. Physiology & Behavior, 57, 1181-1185.
[6] Amit, Z. and Smith, B.R. (1992) Differential Ethanol Intake in Tryon Maze-Bright and Tryon Maze-Dull Rats: Implications for the Validity of the Animal Model of Selectively Bred Rats for High Ethanol Consumption. Psychopharmacology (Berl), 108, 136-140. http://dx.doi.org/10.1007/BF02245298
[7] Satinder, K.P. and Wooldridge, G.E. (1986) Emotional Reactivity and Alcohol Preference among Genetic Crosses of the Maudsley and Roman Rats. Pharmacology Biochemistry and Behavior, 24, 879-881.
[8] Broadhurst, P.I. and Bignami, G. (1964) Correlative Effects of Psychogenetic Selection: A Study of the Roman Highand Low-Avoidance Strains of Rats. Behaviour Research and Therapy, 2, 273-280.
[9] Driscoll, P. and Battig, K. (1982) Behavioral, Emotional and Neurochemical Profiles of Rats Selected for Extreme Differences in Active, Two-Way Avoidance Performance. In: Lieblich, I., Ed., Genetics of the Brain, Elsevier, Amsterdam, 95-123.
[10] Fernández-Teruel, A., Driscoll, P., Gil, L., Aguilar, R., Tobena, A. and Escorihuela, R.M. (2002a) Enduring Effects of Environmental Enrichment on Novelty Seeking, Saccharin and Ethanol Intake in Two Rat Lines (RHA/Verh and RLA/Verh) Differing in Incentive-Seeking Behavior. Pharmacology Biochemistry and Behavior, 73, 225-231.
[11] Manzo, L., Gómez, M.J., Callejas-Aguilera, J.E., Fernández-Teruel, A., Papini, M.R. and Torres, C. (2012) Oral Ethanol Self-Administration in Inbred Roman Highand Low-Avoidance Rats: Gradual versus Abrupt Ethanol Presentation. Physiology & Behavior, 108, 1-5.
[12] Razafimanalina, R., Mormède, P. and Velley, L. (1996) Gustatory Preference-Aversion Profiles for Saccharin, Quinine and Alcohol in Roman Highand Low-Avoidance Lines. Behavioural Pharmacology, 7, 78-84.
[13] Escorihuela, R.M., Fernández-Teruel, A., Gil, L., Aguilar, R., Tobena, A. and Driscoll, P. (1999) Inbred Roman Highand Low-Avoidance Rats: Differences in Anxiety, Novelty-Seeking, and Shuttlebox Behaviors. Physiology & Behavior, 67, 19-26. http://dx.doi.org/10.1016/S0031-9384(99)00064-5
[14] Giorgi, O., Lecca, D., Piras, G., Driscoll, P. and Corda, M.G. (2003a) Dissociation between Mesocortical Dopamine Release and Fear-Related Behaviors in Two Psychogenetically Selected Lines of Rats That Differ in Coping Strategies to Aversive Conditions. European Journal of Neuroscience, 17, 2716-2726.
[15] Moreno, M., Cardona, D., Gómez, M.J., Sánchez-Santed, F., Tobena, A., Fernández-Teruel, A., Campa, L., Sunol, C., Escarabajal, M.D., Torres, C. and Flores, P. (2010) Impulsivity Characterization in the Roman High- and Low- Avoidance Rat Strains: Behavioral and Neurochemical Differences. Neuropsychopharmacology, 35, 1198-1208.
[16] Siegel, J. (1997) Augmenting and Reducing of Visual Evoked Potentials in High- and Low-Sensation Seeking Humans, Cats, and Rats. Behavior Genetics, 27, 557-563.
[17] Steimer, T. and Driscoll, P. (2003) Divergent Stress Responses and Coping Styles in Psychogenetically Selected Roman High-(RHA) and Low-(RLA) Avoidance Rats: Behavioural, Neuroendocrine and Developmental Aspects. Stress, 6, 87-100.
[18] Steimer, T. and Driscoll, P. (2005) Inter-Individual vs Line/Strain Differences in Psychogenetically Selected Roman High-(RHA) and Low-(RLA) Avoidance Rats: Neuroendocrine and Behavioural Aspects. Neuroscience & Biobehavioral Reviews, 29, 99-112.
[19] Boersma, G.J., Benthem, L., van Dijk, G. and Scheurink, A.J. (2011) Individual Variation in the (Patho)Physiology of Energy Balance. Physiology & Behavior, 103, 89-97.
[20] Fernández-Teruel, A., Escorihuela, R.M., Gray, J.A., Aguilar, R., Gil, L., Giménez-Llort, L., Tobena, A., Bhomra, A., Nicod, A., Mott, R., Driscoll, P., Dawson, G.R. and Flint, J. (2002b) A Quantitative Trait Locus Influencing Anxiety in the Laboratory Rat. Genome Research, 12, 618-626.
[21] Ferré, P., Fernández-Teruel, A., Escorihuela, R.M., Driscoll, P., Corda, M.G., Giorgi, O. and Tobena, A. (1995) Behavior of the Roman/Verh Highand Low-Avoidance Rat Lines in Anxiety Tests: Relationship with Defecation and Self- Grooming. Physiology & Behavior, 58, 1209-1213.
[22] Gentsch, C., Lichtsteiner, M. and Feer, H. (1991) Genetic and Environmental Influences on Reactive and Spontaneous Locomotor Activities in Rats. Experientia, 47, 998-1008.
[23] López-Aumatell, R., Vicens-Costa, E., Guitart-Masip, M., Martínez-Membrives, E., Valdar, W., Johannesson, M., Canete, T., Blázquez, G., Driscoll, P., Flint, J., Tobena, A. and Fernández-Teruel, A. (2009) Unlearned Anxiety Predicts Learned Fear: A Comparison among Heterogeneous Rats and the Roman Rat Strains. Behavioural Brain Research, 202, 92-101.
[24] Piras, G., Piludu, M.A., Giorgi, O. and Corda, M.G. (2014) Effects of Chronic Antidepressant Treatments in a Putative Genetic Model of Vulnerability (Roman Low-Avoidance Rats) and Resistance (Roman High-Avoidance Rats) to Stress-Induced Depression. Psychopharmacology, 231, 43-53.
[25] Carrasco, J., Márquez, C., Nadal, R., Tobena, A., Fernández-Teruel, A. and Armario, A. (2008) Characterization of Central and Peripheral Components of the Hypothalamus-Pituitary-Adrenal Axis in the Inbred Roman Rat Strains. Psychoneuroendocrinology, 33,437-445.
[26] Gentsch, C., Lichtsteiner, M., Driscoll, P. and Feer, H. (1982) Differential Hormonal and Physiological Responses to Stress in Roman Highand Low-Avoidance Rats. Physiology & Behavior, 28, 259-263.
[27] Steimer, T., Python, A., Schulz, P.E. and Aubry, J.M. (2007) Plasma Corticosterone, Dexamethasone (DEX) Suppression and DEX/CRH Tests in a Rat Model of Genetic Vulnerability to Depression. Psychoneuroendocrinology, 32, 575-579. http://dx.doi.org/10.1016/j.psyneuen.2007.03.012
[28] Giorgi, O., Piras, G. and Corda, M.G. (2007) The Psychogenetically Selected Roman High- and Low-Avoidance Rat Lines: A Model to Study the Individual Vulnerability to Drug Addiction. Neuroscience & Biobehavioral Reviews, 31, 148-163. http://dx.doi.org/10.1016/j.neubiorev.2006.07.008
[29] Lecca, D., Piras, G., Driscoll, P., Giorgi, O. and Corda, M.G. (2004) A Differential Activation of Dopamine Output in the Shell and Core of the Nucleus Accumbens Is Associated with the Motor Responses to Addictive Drugs: A Brain Dialysis Study in Roman High- and Low-Avoidance Rats. Neuropharmacology, 46, 688-699.
[30] Fattore, L., Piras, G., Corda, M.G. and Giorgi, O. (2009) The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration. Neuropsychopharmacology, 34, 1091-1101.
[31] Agabio, R., Cortis, G., Fadda, F., Gessa, G.L., Lobina, C., Reali, R. and Colombo, G. (1996) Circadian Drinking Pattern of Sardinian Alcohol-Preferring Rats. Alcohol and Alcoholism, 31, 385-388.
[32] Colombo, G., Lobina, C., Carai, M.A. and Gessa, G.L. (2006) REVIEW: Phenotypic Characterization of Genetically Selected Sardinian Alcohol-Preferring (sP) and -Non-Preferring (sNP) Rats. Addiction Biology, 11, 324-338.
[33] Imperato, A. and Di Chiara, G. (1986) Preferential Stimulation of Dopamine Release in the Nucleus Accumbens of Freely Moving Rats by Ethanol. Journal of Pharmacology and Experimental Therapeutics, 239, 219-228.
[34] Yoshimoto, K., McBride, W.J., Lumeng, L. and Li, T.K. (1992) Alcohol Stimulates the Release of Dopamine and Serotonin in the Nucleus Accumbens. Alcohol, 9, 17-22.
[35] Yim, H.J., Schallert, T., Randall, P.K. and Gonzales, R.A. (1998) Comparison of Local and Systemic Ethanol Effects on Extracellular Dopamine Concentration in Rat Nucleus Accumbens by Microdialysis. Alcoholism: Clinical & Experimental Research, 22, 367-374. http://dx.doi.org/10.1111/j.1530-0277.1998.tb03662.x
[36] Pontieri, F.E., Tanda, G. and Di Chiara, G (1995) Intravenous Cocaine, Morphine, and Amphetamine Preferentially Increase Extracellular Dopamine in the “Shell” as Compared with the “Core” of the Rat Nucleus Accumbens. Proceedings of the National Academy of Sciences of the United Statesd of America, 92, 12304-12308.
[37] Bustamante, D., Quintanilla, M.E., Tampier, L., Gonzalez-Lira, V., Israel, Y. and Herrera-Marschitz, M. (2008) Ethanol Induces Stronger Dopamine Release in Nucleus Accumbens (Shell) of Alcohol-Preferring (Bibulous) than in Alcohol-Avoiding (Abstainer) Rats. European Journal of Pharmacology, 591, 153-158.
[38] Giorgi, O., Piras, G., Lecca, D. and Corda, M.G. (2005) Differential Activation of Dopamine Release in the Nucleus Accumbens Core and Shell after Acute or Repeated Amphetamine Injections: A Comparative Study in the Roman High- and Low-Avoidance Rat Lines. Neuroscience, 135, 987-998.
[39] Paxinos, G. and Watson, C. (1998) The Rat Brain in Stereotaxic Coordinates. Academic Press, Sydney.
[40] Overstreet, D.H., Halikas, J.A., Seredenin, S.B., Kampov-Polevoy, A.B., Viglinskaya, I.V., Kashevskaya, O., Badishtov, B.A., Knapp, D.J., Mormede, P., Kiianmaa, K., Li, T.K. and Rezvani, A.H. (1997) Behavioral Similarities and Differences among Alcohol-Preferring and -Nonpreferring Rats: Confirmation by Factor Analysis and Extension to Additional Groups. Alcoholism: Clinical and Experimental Research, 21, 840-848.
[41] Corda, M.G., Lecca, D., Piras, G., Viola, H., Medina, J.H. and Giorgi, O. (2001) Voluntary Ethanol Intake Activates Meso-Accumbal Dopaminergic Transmission in Roman High-Avoidance, but Not Roman Low-Avoidance Rats. Journal of Neurochemistry, 78, 80.
[42] Rossetti, Z.L., Melis, F., Carboni, S., Diana, M. and Gessa, G.L. (1992) Alcohol Withdrawal in Rats Is Associated with a Marked Fall in Extraneuronal Dopamine. Alcoholism: Clinical and Experimental Research, 16, 529-532.
[43] Weiss, F., Parsons, L.H., Schulteis, G., Hyytia, P., Lorang, M.T., Bloom, F.E. and Koob, G.F. (1996) Ethanol SelfAdministration Restores Withdrawal-Associated Deficiencies in Accumbal Dopamine and 5-Hydroxytryptamine Release in Dependent Rats. The Journal of Neuroscience, 16, 3474-3485.
[44] Vanderschuren, L.J. and Kalivas, P.W. (2000) Alterations in Dopaminergic and Glutamatergic Transmission in the Induction and Expression of Behavioral Sensitization: A Critical Review of Preclinical Studies. Psychopharmacology, 151, 99-120. http://dx.doi.org/10.1007/s002130000493
[45] Nestby, P., Vanderschuren, L.J., De Vries, T.J., Hogenboom, F., Wardeh, G., Mulder, A.H. and Schoffelmeer, A.N. (1997) Ethanol, Like Psychostimulants and Morphine, Causes Long-Lasting Hyperreactivity of Dopamine and Acetylcholine Neurons of Rat Nucleus Accumbens: Possible Role in Behavioural Sensitization. Psychopharmacology, 133, 69-76.
[46] Robinson, T.E. and Berridge, K.C. (2001) Incentive-Sensitization and Addiction. Addiction, 96, 103-114.
[47] Zeier, H., Baettig, K. and Driscoll, P. (1978) Acquisition of DRL-20 Behavior in Male and Female, Roman High- and Low-Avoidance Rats. Physiology & Behavior, 20, 791-793.
[48] Giorgi, O., Valentini, V., Piras, G., Di Chiara, G. and Corda, M.G. (1999). Palatable Food Differentially Activates Dopaminergic Function in the CNS of Roman/Verh Lines and Strains of Rats. Society for Neuroscience Meeting Abstract Book, 25, 2152.
[49] Piras, G., Lecca, D., Corda, M.G. and Giorgi, O. (2003) Repeated Morphine Injections Induce Behavioural Sensitization in Roman Highbut Not in Roman Low-Avoidance Rats. NeuroReport, 14, 2433-2438.
[50] Corda, M.G., Piras, G., Lecca, D., Fernández-Teruel, A., Driscoll, P. and Giorgi, O. (2005) The Psychogenetically Selected Roman Rat Lines Differ in the Susceptibility to Develop Amphetamine Sensitization. Behavioural Brain Research, 157,147-156. http://dx.doi.org/10.1016/j.bbr.2004.06.016
[51] Giorgi, O., Piras, G., Lecca, D. and Corda, M.G. (2005) Behavioural Effects of Acute and Repeated Cocaine Treatments: A Comparative Study in Sensitisation-Prone RHA Rats and Their Sensitisation-Resistant RLA Counterparts. Psychopharmacology, 180, 530-538. http://dx.doi.org/10.1007/s00213-005-2177-7
[52] Zuckerman, M. (1994) Behavioral Expressions and Biosocial Bases of Sensation Seeking. Cambridge University Press, New York.
[53] Bardo, M.T., Donohew, R.L. and Harrington, N.G. (1996) Psychobiology of Novelty Seeking and Drug Seeking Behavior. Behavioural Brain Research, 77, 23-43. http://dx.doi.org/10.1016/0166-4328(95)00203-0
[54] Flagel, S.B., Robinson, T.E., Clark, J.J., Clinton, S.M., Watson, S.J., Seeman, P., Phillips, P.E. and Akil, H. (2010) An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction. Neuropsychopharmacology, 35, 388-400. http://dx.doi.org/10.1038/npp.2009.142
[55] Meyer, A.C., Rahman, S., Charnigo, R.J., Dwoskin, L.P., Crabbe, J.C. and Bardo, M.T. (2010) Genetics of Novelty Seeking, Amphetamine Self-Administration and Reinstatement Using Inbred Rats. Genes, Brain and Behavior, 9, 790-798. http://dx.doi.org/10.1111/j.1601-183X.2010.00616.x
[56] Nadal, R., Armario, A. and Janak, P.H. (2002) Positive Relationship between Activity in a Novel Environment and Operant Ethanol Self-Administration in Rats. Psychopharmacology, 3, 333-338.
[57] Manzo, L., Gómez, M.J., Callejas-Aguilera, J.E., Donaire, R., Sabariego, M., Fernández-Teruel, A., Canete, A., Blázquez, G., Papini, M.R. and Torres, C. (2014) Relationship between Ethanol Preference and Sensation/Novelty Seeking. Physiology & Behavior, 133, 53-60.
[58] Kabbaj, M. (2006) Individual Differences in Vulnerability to Drug Abuse: The High Responders/Low Responders Model. CNS & Neurological Disorders, Drug Targets, 5, 513-520.
[59] Giorgi, O., Orlandi, M., Escorihuela, R.M., Driscoll, P., Lecca, D. and Corda, M.G. (1994) GABAergic and Dopaminergic Transmission in the Brain of Roman High-Avoidance and Roman Low-Avoidance Rats. Brain Research, 638, 133-138. http://dx.doi.org/10.1016/0006-8993(94)90642-4
[60] Giorgi, O., Piras, G., Lecca, D., Hansson, S., Driscoll, P. and Corda, M.G. (2003) Differential Neurochemical Properties of Central Serotonergic Transmission in Roman Highand Low-Avoidance Rats. Journal of Neurochemistry, 86, 422-431. http://dx.doi.org/10.1046/j.1471-4159.2003.01845.x

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