Abstract
Drug addiction includes two important characteristics, chronic compulsive or uncontrollable drug use and a withdrawal syndrome when use of the drug is stopped. Animal models for the motivational components of drug dependence have been developed allowing a systematic exploration of the neurobiological mechanisms of drug dependence. The reinforcing actions of acute cocaine as measured by intravenous cocaine self-administration appear to be mediated by the presynaptic release of dopamine in the region of the nucleus accumbens and may preferentially involve the dopamine D-1 receptor subtype. The nucleus accumbens circuitry involved in the reinforcing actions of cocaine may include the ventral pallidum and may be modulated by serotonin. Chronic cocaine produces increases in brain reward thresholds that may reflect the “dysphoria” and anhedonia associated with cocaine dependence and suggests a dysregulation of brain reward systems possibly involving dopamine. Reliable measures for the acute reinforcing effects of ethanol in nondependent animals have been established in the rat using a lever press operant and a taste habituation procedure. Important roles have been established for serotonin, GABA, dopamine, and opioids in the acute reinforcing properties of ethanol, perhaps acting on some of the same neural circuitry subsuming the reinforcing actions of other drugs of abuse. Studies of the motivational aspects of ethanol dependence have suggested a functional role for brain corticotropin-releasing factor. These results suggest that the neurobiology of drug dependence involves not only neurotransmitters that mediate the acute reinforcing properties of drugs, but also the aversive motivational and emotional aspects of drug withdrawal. Advances in our understanding of brain changes associated with the switch from acute effects to chronic actions may provide a key to our understanding of not only drug dependence, but also psychopathology such as, anxiety, and affective disorders.
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References
Nelson JE, Pearson HW, Sayer N, Glenn TJ: Guide to Drug Abuse Research Terminology. US Department of Health and Human Services, Washington, DC, 1980.
Eddy NB, Halbach H, Ksbell H, Seevers MH: Drug dependence, its significance and characteristics. Bull WHO 32:721–723, 1965.
Koob GF, Bloom FE: Cellular and molecular mechanisms of drug dependence. Science 242:715–723, 1988.
Sparber SB, Meyer DR: Clonidine antagonizes naloxone induced suppression of conditioned behavior and bodyweight loss in morphine dependent rats. Pharmacol Biochem Behav 9:319–325, 1978.
Denoble U, Begleiter H: Response suppression on a mixed schedule of reinforcement during alcohol withdrawal. Pharmacol Biochem Behav 5:227–229, 1976.
Kokkinidis L, Zacharko RM, Predy PA: Post-amphetamine depression of self-stimulation responding from the substantia nigra: reversal by tricyclic antidepressants. Pharmacol Biochem Behav 13:379–383, 1980.
Kokkinidis L, Zacharko RM, Anisman H: Amphetamine withdrawal: a behavioral evaluation. Life Sci 38:1617–1623, 1986.
Markou MA, Koob GF: Postcocaine anhedonia: an animal model of cocaine withdrawal. Neuropsychopharmacology 4:17–26, 1991.
Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT: CRF antagonist blocks alcohol withdrawal “anxiogenic” response. Psychopharmacology 103:227–232, 1991.
Stinus L, Le Moal M, Koob GF: The nucleus accumbens and amygdala as possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37:767–773, 1990.
Fischman MW, Schuster CR, Hatano Y: A comparison of the subjective and cardiovascular effects of cocaine and lidocaine in humans. Pharmacol Biochem Behav 18:123–127, 1983.
Groppetti A, Zambotti F, Biazzi A, Mantegazza P: Amphetamine and cocaine on amine turnover, in Usdin E, Snyder SH (eds): Frontiers in Catecholamine Research. Oxford, Pergamon Press, 1973, p 917.
Spealman RD, Goldberg SR, Kelleher RT, Goldberg DM, Charlton JP: Some effects of cocaine and two cocaine analogs on schedule controlled behavior of squirrel monkeys. J Pharmacol Exp Ther 202:500–509, 1977.
Kornetsky C, Esposito RU: Reward and detection thresholds for brain stimulation: dissociative effects of cocaine. Brain Res 209:496–500, 1981.
Pickens R, Thompson T: Cocaine reinforced behavior in rats: effects of reinforcement magnitude and fixed ratio size. J Pharmacol Exp Ther 161:122–129, 1968.
Simon P: Psychopharmacological profile of cocaine, in Usdin E, Snyder SH (eds): Frontiers of Catecholamine Research. Oxford, Pergamon Press, 1973, p 1043.
Randrup A, Munkvad I: Biochemical, anatomical and psychological investigations of stereotyped behavior induced by amphetamines, in Costa E, Garahini S (eds): Amphetamines and Related Compounds. New York, Raven Press, 1970, p 695.
Kornetsky C, Esposito RU: Euphorigenic drugs: effects on reward pathways of the brain. Fed Proc 38:2473–2476, 1979.
Kornetsky C, Bain G: Biobehavioral bases of the reinforcing properties of opiate drugs. Ann NY Acad Sci 398:240–259, 1982.
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ: Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223, 1987.
Kelly PH, Seviour PW, Iversen SD: Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522, 1975.
Kelly PH, Iversen SD: Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Eur J Pharmacol 40:45–56, 1976.
Roberts DCS, Zis AP, Fibiger HC: Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine. Brain Res 93:441–454, 1975.
Joyce EM, Koob GF: Amphetamine-, scopolamine-, and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology 73:311–313, 1981.
Vaccarino FJ, Amalric M, Swerdlow NR, Koob GF: Blockade of amphetamine-but not opiateinduced locomotion following antagonism of dopamine function in the rat. Pharmacol Biochem Behav 24:61–65, 1986.
Swerdlow NR, Koob GF: Separate neural substrates of the locomotor-activating properties of amphetamine, caffeine and corticotropin releasing factor (CRF) in the rat. Pharmacol Biochem Behav 23:303–307, 1985.
Jonsson LE, Anggard E, Gunne LM: Blcokade of intravenous amphetamine euphoria in man. Clin Pharmacol Ther 12:889–896, 1971.
Pickens R, Meisch RA, Dougherty JA: Chemical interactions in amphetamine reinforcement. Psychol Rep 23:1267–1270, 1968.
Risner M, Jones BE: Role of noradrenergic and dopaminergic processes in amphetamine self-administration. Pharmacol Biochem Behav 5:477–482, 1976.
Yokel RA, Wise RA: Attenuation of intravenous amphetamine reinforcement by central dopamine blockade in rats. Psychopharmacology 48:311–318, 1976.
De Wit H, Wise RA: Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide, but not with the noradrenergic blockers phentolamine and phenoxybenzamine. Can J Psychol 31:195–203, 1977.
Yokel RA, Wise RA: Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science 187:547–549, 1975.
Ettenberg A, Pettit HO, Bloom FE, Koob GF: Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacology 78:204–209, 1982.
Roberts DCS, Vickers G: Atypical neuroleptics increase self-administration of cocaine: an evaluation of a behavioral screen for antipsychotic activity. Psychopharmacology 82:135–139, 1984.
Koob GF, Le HT, Creese I: D-1 receptor antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci Lett 79:315–321, 1987.
Roberts DCS, Corcoran ME, Fibiger HC: On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620, 1977.
Lyness WH, Friedle NM, Moore KE: Destruction of dopaminergic nerve terminals in nucleus accumbens: effect on d-amphetamine self-administration. Pharmacol Biochem Behav 11:553–556, 1979.
Roberts DCS, Koob GF, Klonoff P, Fibiger HC: Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787, 1980.
Roberts DCS, Koob GF: Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats. Pharmacol Biochem Behav 17:901–904, 1982.
Martin-Iverson MT, Szostak C, Fibiger HC: 6-hydroxydopamine lesions of the medial prefrontal cortex fail to influence intravenous self-administration of cocaine. Psychopharmacology 88:310–314,1986.
Koob GF, Vaccarino FJ, Amalric M, Bloom FE: Positive reinforcement properties of drugs: search for neural substrates, in Engel J, Oreland L (eds): Brain Reward Systems and Abuse. New York, Raven Press, 1987, p 35.
Le Moal M, Stinus L, Simon H: Increased sensitivity to (+)−amphetamine self-administration by rats following mesocorticolimbic dopamine neurone destruction. Nature 280:156–158, 1979.
Deminiere JM, Simon H, Herman JP, Le Moal M: 6-Hydroxydopamine lesion of the dopamine mesocorticolimbic cell bodies increases (+)−amphetamine self-administration. Psychopharmacology 83:281–284, 1984.
Roberts DCS: Break points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 32:43–47, 1989.
Porrino LJ, Ritz MC, Goodman NL, Sharpe LG, Kuhar MJ, Goldberg SR: Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats. Life Sci 45:1529–1535, 1988.
Carroll ME, Lac ST, Asenio M, Kragh R: Fluoxetine reduces intravenous cocaine self-administration in rats. Pharmacol Biochem Behav 35:237–244, 1990.
Lyness WH: Effect of L-tryptophan pretreatment on d-amphetamine self-administration. Subst Alcohol Actions Misuse 4:305–312, 1983.
Lynn WH, Moore KE: Increased self-administration of d-amphetamine by rats pretreated with meterzoline. Pharmacol Biochem Behav 18:721–724, 1983.
Lyness WH, Friedle NM, Moore KE: Increased self-administration of d-amphetamine after destruction of 5-hydroxytryptaminergic neurons. Pharmacol Biochem Behav 12:937–941, 1980.
Loh EA, Roberts DCS: Break-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin. Psychopharmacology 101:262–266, 1990.
Mogenson GJ, Nielson MA: Evidence that an accumbens to subpallidal GABAergic projection contributes to locomotor activity. Brain Res Bull 11:309–314, 1983.
Swerdlow NR, Koob GF: Neural substrates of apomorphine-stimulated locomotor activity following denervation of the nucleus accumbens. Life Sci 35:2537–2544, 1984.
Zito KA, Vickers G, Roberts DCS: Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens. Pharmacol Biochem Behav 23:1029–1036, 1985.
Hubner CB, Koob GF: The ventral pallidum plays a role in mediating cocaine and heroin self-administration in the rat. Brain Res 508:20–29, 1990.
Gawin FH, Kleber HD: Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Arch Gen Psychiatry 43:107–113, 1986.
Ellinwood EH, Petrie WM: Dependence on amphetamine, cocaine and other stimulants, in Pradhan SN (ed): Drug Abuse: Clinical and Basic Aspects. St. Louis, Mosby, 1977, p 248.
Stellar JR, Stellar E: The Neurobiology of Reward and Motivation. New York, Springer-Verlag, 1985.
Esposito RU, Motola AHD, Kornetsky C: Cocaine: Acute effects on reinforcement thresholds for self-stimulation behavior to the medial forebrain bundle. Pharmacol Biochem Behav 8:437–439, 1978.
Dackis CA, Gold MS: New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 9:469–477, 1985.
Meisch RA: Animal studies of alcohol intake. J Psychiatr Res 141:113–120, 1982.
Meisch RA: Alcohol self-administration in experimental animals, in Smart RG, Glaser FB, Israel Y, Cappel H, Kalant H, Schmidt W, Sellers EM (eds): Research Advances in Alcohol and Drug Problems, 8th ed. New York, Plenum Press, 1984, p 23.
Samson HH: Initiation of ethanol-maintained behavior: a comparison of animal models and their implication of human drinking, in Thompson T, Dews PB, Barrett JE (eds): Neurobehavioral Pharmacology, Vol. 6. Hillsdale, NJ, Lawrence Erlbaum, 1987, p 221.
Stewart RB, Perlanski E, Grupp LA: Ethanol as a reinforcer for rats: factors of facilitation and constraint. Alcohol Clin Exp Res 12:599–608, 1988.
Lester D, Freed EX: Criteria for an animal model of alcoholism. Pharmacol Biochem Behav 1:103–107, 1973.
Mello NK: A review of methods to induce alcohol addiction in animals. Pharmacol Biochem Behav 1:89–101, 1973.
Veale WL: Ethanol selection in the rat following forced acclimation. Pharmacol Biochem Behav 1:233–235, 1973.
Sinclair JD, Senter RJ: Increased preference for ethanol in rats following alcohol deprivation. Psychonom Sci 8:11–12, 1967.
Wayner MJ, Greenberg I: Effects of hypothalamic stimulation, acclimation and periodic withdrawal on ethanol consumption. Physiol Behav 9:737–740, 1972.
Wayner MJ, Greenberg I, Tartaglione R, Nolley D, Fraley S, Cott A: A new factor affecting the consumption of ethyl alcohol and other sapid fluids. Physiol Behav 8:345–362,1972.
Wise RA: Voluntary ethanol intake in rats following exposure to ethanol on various schedules. Psychopharmacology 29:203–210, 1973.
Amit Z, Stern MH: A further investigation of alcohol preference in the laboratory rat induced by hypothalamic stimulation. Psychopharmacologia 21:317–327, 1971.
Eriksson K: Factors affecting voluntary alcohol consumption in the albino rat. Ann Zool Fenniae 6:227–265, 1969.
Falk JL, Samson HH, Tang M: Chronic ingestion techniques for the production of physical dependence on ethanol, in Gross MM (ed): Alcohol Intoxication and Withdrawal. New York, Plenum Press, 1973, p 197.
Pekkanen L, Rusi M: The effects of niacin and riboflavin on voluntary ethanol intake and metabolism in rats. Pharmacol Biochem Behav 11:575–579, 1979.
Samson HS: Initiation of ethanol reinforcement using a sucrose-substitution procedure in food-and water-sated rates. Alcohol Clin Exp Res 10:436–442, 1986.
Falk JL: Production of polydipsia in normal rats by an intermittent food schedule. Science 133:195–196, 1961.
Falk JL, Samson HH, Winger G: Behavioral maintenance of high concentrations of blood ethanol and physical dependence in the rat. Science 177:811–813, 1972.
Meisch RA, Thompson T: Ethanol intake in the absence of concurrent food reinforcement. Psychopharmacologia 22:72–79, 1971.
Meisch RA: Ethanol self-administration: infrahuman studies: in Thompson T, Dews PB (eds): Advances in Behavioral Pharmacology, Vol. 1. New York, Academic Press, 1977.
Meisch RA, Henningfield JE: Drinking of ethanol by rhesus monkeys: experimental strategies for establishing ethanol as a reinforcer. Adv Exp Med Biol 85:443–463, 1977.
Steward RB, Grupp LA: A simplified procedure for producing ethanol self-administration in rats. Pharmacol Biochem Behav 21:255–258, 1984.
Linseman MA: Alcohol consumption in free-feeding rats: procedural, genetic and pharmaco-kinetic factors. Psychopharmacology 92:254–261, 1987.
Linseman MA: Alcohol consumption in free-feeding rats—procedural and genetic factors. Soc Neurosci Abstr 12:279–279, 1986.
Roehrs TA, Samson HH: Relative responding on concurrent schedules: indexing ethanol’s reinforcing efficacy. Pharmacol Biochem Behav 16:393–396, 1982.
Grant KA, Samson HH: Induction and maintenance of ethanol self-administration without food deprivation in the rat. Psychopharmacology 86:475–479, 1985.
Weiss F, Mitchiner M, Bloom FE, Koob GF: Free-choice responding for ethanol versus water in alcohol-preferring (P) and unselected Wistar rats is differentially altered by naloxone, bromocriptine and methysergide. Psychopharmacology 101:178–186, 1990.
Lumeng, L, Waller MB, McBride WJ, Li TK: Different sensitivities to ethanol in alcohol-preferring and nonpreferring rats. Pharmacol Biochem Behav 16:501–507, 1982.
Lumeng L, Li T-K: The development of metabolic tolerance in the alcohol-preferring P rats: comparison of forced and free-choice drinking of ethanol. Pharmacol Biochem Behav 25:1013–1020, 1986.
Ferko AP, Bobyock E: Rates of ethanol disappearance from blood and hypothermia following acute and prolonged ethanol inhalation. Toxicol Appl Pharmacol 50:417–427, 1979.
York JL: A comparison of the discriminative stimulus properties of ethanol, barbital, and phenobarbital in rats. Psychopharmacology 60:19–23,1978.
Imperato A, DiChaira G: Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 239:219–239, 1986.
Waller MB, Murphy JM, McBride WJ, Lumeng L, Li T-K: Effect of low-dose ethanol on spontaneous motor activity in alcohol-preferring and nonpreferring rats. Pharmacol Biochem Behav 24:617–623, 1986.
Li T-K, Lumeng L, McBride WJ, Waller MB, Murphy JM: Studies on animal model of alcoholism, in Braude E, Chao HM (eds): Genetic and Biological Markers in Drug Abuse and Alcoholism, National Institute on Drug Abuse Research Monograph. Rockville, MD, NIDA, 1986, p 41.
Altshuler HL, Phillips PE, Feinhandler DA: Alterations of ethanol self-administration by naltrexone. Life Sci 26:679–688, 1980.
Marfaing-Jallat P, Miceli D, LeMagnen J: Decrease in ethanol consumption by naloxone in naive and dependent rats. Pharmacol Biochem Behav 18:5355–5395, 1983.
Myers RD, Critcher EC: Naloxone alters alcohol drinking induced in the rat by tetrahydropapaveroline (THP) infused ICY Pharmacol Biochem Behav 16:827–836,1982.
Pulvirenti L, Kastin AJ: Naloxone, but not Tyr-MIF-1, reduces volitional ethanol drinking in rats: correlation with degree of spontaneous preferences. Pharmacol Biochem Behav 31:129–129, 1988.
Reid LD, Hunter GA: Morphine and naloxone modulate intake of ethanol. Alcohol 1:33–37, 1984.
Sandi C, Borell J, Guzaz C: Naloxone decreases ethanol consumption within a free choice paradigm in rats. Pharmacol Biochem Behav 29:39–43, 1988.
Volpicelli R, Davis MA, Olgin JE: Naltrexone blocks the post-shock increase of ethanol consumption. Life Sci 38:841–847, 1986.
Hunter GA, Beaman CM, Dunn LL, Reid LD: Selected opioids, ethanol and intake of alcohol. Alcohol 1:43–46, 1984.
Mudar PJ, LeCann NC, Czirr SA, Hubbell CL, Reid LD: Methadone, pentobarbital, pimozide and ethanol-intake. Alcohol 3:303–308, 1986.
Hubbell CL, Czirr SA, Reid LD: Persistence and specificity of small doses of morphine on intake of alcoholic beverages. Alcohol 4:149–156, 1987.
Czirr SA, Hubbell CL, Milano WC, Frank JM, Reid LD: Selected opioids modify intake of sweetened ethanol solution among female rats. Alcohol 4:157–160, 1987.
Beaman CM, Hunter GA, Dunn LL, Reid LD: Opioids, benzodiazepines and intake of ethanol. Alcohol 1:39–42, 1984.
Reid LD, Czirr SA, Bensinger CC, Hubbell CL, Volanth AJ: Morphine and diprenorphine together potentiate intake of alcoholic beverages. Alcohol 4:161–168, 1987.
Samson HH, Doyle TF: Oral ethanol self-administration in the rat: effects of naloxone. Pharmacol Biochem Behav 22:91–99, 1985.
Brown DR, Holtzman SG: Suppression of deprivation-induced food and water intake in rats and mice by naloxone. Pharmacol Biochem Behav 11:567–573, 1979.
Frenk H, Rogers GH: The suppressant effects of naloxone on food and water intake in the rat. Behav Neural Biol 26:23–40, 1979.
Holtzman SG: Suppression of appetitive behavior in the rat by naloxone: lack of effect of prior morphine dependence. Life Sci 24:219–226, 1979.
Hynes MA, Gallagher M, Yacos KV: Systemic and intraventricular naloxone administration: effects on food and water intake. Behav Neural Biol 32:334–342, 1981.
Cooper SJ: Naloxone: Effects on food and water consumption in the non-deprived and deprived rat. Psycho-pharmacology 71(1):1–6, 1980.
Ostrowski NL, Foley TL, Lind MD, Reid LD: Naloxone reduces fluid intake: effects of food and water deprivation. Pharmacol Biochem Behav 12:431–435, 1980.
Stapleton JM, Ostrowski NL, Merriman VJ, Lind MD, Reid LD: Naloxone reduces fluid consumption in deprived and nondeprived rats. Bull Psychon Soc 13:237–239, 1979.
Amit S, Sutherland EA, Bill K, Ogren SO: Zimelidine: a review of its effects on ethanol consumption. Neurosci Biobehav Rev 8:35–54, 1984.
Daoust M, Chretien P, Moore N, Saligaut C, Lhuintre JP, Boismare F: Isolation and striatal (3H) serotonin uptake: role in the voluntary intake of ethanol by rats. Pharmacol Biochem Behav 22:205–208, 1985.
Geller I: Effects of para-chlorophenylalanine and 5-hydroxytryptophane on alcohol intake in rats. Pharmacol Biochem Behav 1:361–365, 1973.
Khanna JM, Kalant H, Le AD, Mayer J, LeBlanc AE: Effect of modification of brain serotonin (5-HT) on ethanol tolerance. Alcohol Clin Exp Res 3:353–358, 1979.
Lawrin MO, Naranjo CA, Sellers EM: Identification of new drugs for modulating alcohol consumption. Psycnopharmacol Bull 22:1020–1025, 1986.
Myers RD, Martin GE: The role of cerebral serotonin in the ethanol preference of animals. Ann NY Acad Sci 215:135–144, 1973.
Rockman GE, Amit Z, Carr G, Brown ZW, Ogren SO: Attenuation of ethanol by 5-hydroxytryptamine blockade in laboratory rats. I. Involvement of brain 5-hydroxytryptamine in the mediation of positive reinforcing properties of ethanol. Arch Int Pharmacodyn Ther 241:245–259, 1979.
Zabik JE, Blinkerd K, Roache JD: Serotonin and ethanol aversion in the rat, in Naranjo CA, Sellers EM (eds): Research Advances in New Psychopharmacological Treatments of Alcoholism. New York, Excerpta Medica, 1985, p 87.
Frey H-H, Magnussen MP, Kaergaard Nielsen C: The effect of p-chloroamphetamine on the consumption of ethanol by rats. Arch Int Pharmacodyn Ther 183:165–172, 1970.
Myers RD, Veale WL: Alcohol preference in the rat: reduction following depletion of brain serotonin. Science 160:1469–1471, 1968.
Opitz K: Beobachtungen bei Alkohol trinkenden Ratten—Einfluss von Fenfluramin. Pharmacopsykiat Neuropychopharmakol 2:202–205, 1969.
Veale WL, Myers RD: Decrease in ethanol intake in rats following administration of p-chlorophenylalanine. Neuropharmacology 9:317–326, 1970.
Nachman M, Lester D, LeMagnen J: Alcohol aversion in the rat: behavioral assessment of noxious drug effects. Science 168:1244–1246, 1970.
Parker LF, Radow BL: Effects of parachlorophenylalanine on ethanol self-selection in the rat. Pharmacol Biochem Behav 4:535–540, 1976.
Stein JM, Wayner MJ, Tilson HA: The effect of parachlorophenylalanine on the intake of alcohol and saccharin solutions. Pharmacol Biochem Behav 6:117–122, 1977.
Ahlenius S, Carlsson A, Engel J, Svensson T, Sodersten P: Antagonism by alpha methyltyrosine of the ethanol-induced stimulation and euphoria in man. Clin Pharmacol Ther 14:586–591, 1973.
Amit Z, Brown ZW, Levitan DE, Ogren SO: Noradrenergic mediation of the positive reinforcing properties of ethanol. I. Suppression of ethanol consumption in laboratory rats following dopamine-beta-hydroxylase inhibition. Arch Int Pharmacodyn Ther 230:76–82, 1977.
Amit Z, Levitan DE, Lindros KO: Suppression of ethanol intake following administration of dopamine-beta-hydroxylase inhibitors in rats. Arch Int Pharmacol Ther 223:114–119, 1976.
Davis WM, Werner TE, Smith SG: Reinforcement with intragastric infusions of ethanol: blocking effect of FLA-57. Pharmacol Biochem Behav 11:545–548, 1979.
Pfeffer AO, Samson HH: Haloperidol and apomorphine effects on ethanol reinforcement in free-feeding rats. Pharmacol Biochem Behav 29:343–350, 1988.
Pfeffer AO, Samson HH: Oral ethanol reinforcements: interactive effects of amphetamine, pimozide and food restriction. Alcohol Drug Res 6:37–48, 1985.
Pfeffer AO, Samson HH: Effect of pimozide on home cage ethanol drinking in the rat: dependence on drinking session length. Drug Alcohol Depend 17:47–55, 1986.
Rassnick S, Pulvirenti L, Koob GF: Effects of a novel dopamine agonist, Sandoz 205-152, on ethanol self-administration. Soc Neurosci Abstr 15:251, 1989.
Hubner CB, Koob GF: Bromocriptine produces decreases in cocaine self-administration in the rat. Neuropsychopharmacology 3:101–108, 1990.
Liljequist S, Engel JA: The effects of GABA and benzodiazepine receptor antagonists on the anti-conflict actions of diazepam or ethanol. Pharmacol Biochem Behav 21:521–525, 1984.
Koob GF, Mendelson WB, Schafer J, Wall TL, Thatcher-Britton K, Bloom FE: Picrotoxin receptor ligard blocks anti-punishment effects of alcohol. Alcohol 5:437–443, 1988.
Frye GD, Brese GR: GABAergic modulation of ethanol-induced motor impairment. J Pharmacol Exp Ther 223:750–756, 1982.
Liljequist S, Engel J: Effects of GABAergic agonists and antagonists on various ethanolinduced behavioral changes. Psychopharmacology 78:71–75, 1982.
Becker HC, Anton RF: Valproate potentiates and picrotoxin antagonizes the anxiolytic action of ethanol in a nonshock conflict task. Neuropharmacology 29:837–843, 1990.
Suzdak PD, Schwartz RD, Skolnick P, Paul SM: Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosome. Proc Natl Acad Sci USA 83:4071–4075, 1986.
Allan AM, Harris RA: Acute and chronic ethanol treatments alter GABA receptor-operated chloride channels. Pharmacol Biochem Behav 27:665–670, 1987.
Boismare F, Daoust M, Moore N, Saligaut C, Lhuintre JP, Chretien P, Durlach J: A homotaurine derivative reduces the voluntary intake of ethanol by rats: area cerebral GABA receptors involved. Pharmacol Biochem Behav 21:787–789, 1984.
Fuchs V, Burbes E, Cooper H: The influence of haloperidol and amino-oxyacetic acid on etonitazene, alcohol, diazepam and barbital consumption. Drug Alcohol Depend 14:179–186, 1984.
Deutsch JA, Walton NY: Diazepam maintenance of alcohol preference during alcohol withdrawal. Science 198:307–309, 1977.
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM: A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 236:1243–1247, 1986.
Britton KT, Ehlers CL, Koob GF: Is ethanol antagonist Rol5-4513 selective for ethanol? Science 239:648–650, 1988.
Samson HH, Tolliver GA, Pfeffer AO, Sadeghi KG, Mills FG: Oral ethanol reinforcement in the rat: effect of the partial inverse benzodiazepine agonist R015-4513. Pharmacol Biochem Behav 27:517–519, 1987.
Gianoulakis C: The effect of ethanol on the biosynthesis and regulation of opioid peptides. Experientia 45:428–435, 1989.
Naber D, Soble MG, Pickar D: Ethanol increases opioid activity in plasma of normal volunteers. Pharmacopsychiatry 14:160–161, 1981.
Patel VA, Pohorecky LA: Acute and chronic ethanol treatment on beta-enorphin and catecholamine levels. Alcohol 6:59–63, 1989.
Schultz R, Wuster M, Duka T, Herz A: Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. Psychopharmacology 68:221–227, 1980.
Seizinger BR, Bovermann K, Moysinger D, Hollt V, Herz A: Differential effect of acute and chronic ethanol treatment on particular opioid peptide systems in discrete regions of the rat brain and pituitary. Pharmacol Biochem Behav 18:361–369, 1983.
Genazzani AR, Nappi G, Facchinetti F, Mazella GL, Parrini D, Sinforiani E, Petraglia F, Savoldi F: Central deficiency of b-endorphin in alcohol addicts. J Clin Endocrinol Metab 55:583–586, 1982.
Froehlich JC, Harts J, Lumeng L, Li T-K: Naloxone attenuation of voluntary alcohol consumption. Alcohol Alcohol Suppl 1:333–337, 1987.
Blum K, Briggs AH, DeLallo L, Elston SFA, Ochoa R: Whole brain methionine enkephalinase of ethanol-avoiding and ethanol-preferring C57B1 mice. Experientia 38:1469–1470, 1982.
Khanna JM, Le AD, Kalant H, LeBlanc AE: Role of serotonin (5-HT) in tolerance to ethanol and barbiturates, in Begleiter H (ed): Biological Effects of Alcohol. New York, Plenum Press, 1980, p 181.
Le AD, Khanna JM, LeBlanc AE: Effect of modification of brain serotonin (5-HT), norepinephrine (NE) and dopamine (DA) on ethanol tolerance. Psychopharmacology 75:231–235, 1981.
Gongwer MA, Murphy JM, McBride WJ, Lumeng L, Li TK: Regional brain contents of serotonin, dopamine and their metabolites in the selectively bred high-and low-alcohol drinking lines of rats. Alcohol 6:317–320, 1989.
Murphy JM, McBride WJ, Lumeng L, Li T-K: Regional brain levels of monoamines in alcoholpreferring and non-preferring lines of rats. Pharmacol Biochem Behav 16:145–149, 1982.
Murphy JM, McBride WJ, Lumeng L, Li T-K: Contents of monoamines in forebrain regions of alcohol-preferring (P) and non-preferring (NP) lines of rats. Pharmacol Biochem Behav 26:389–392, 1987.
Yoshimoto K, Komura S: Re-examination of the relationship between alcohol preference and brain monoamines in inbred strains of mice including senescence-accelerated mice. Pharmacol Biochem Behav 27:317–322, 1987.
Yoshimoto K, Komura S, Mizohata K: Alcohol preference and brain monoamines in five inbred strains of mice. IRCS Med Sci 13:1192–1193, 1985.
McBride WJ, Murphy JM, Lumeng L, Li T-K: Effects of Ro-15-4513, fluoxetine and desipramine on the intake of ethanol, water and food by the alcohol-preferring (P) and non-preferring (NP) lines of rats. Pharmacol Biochem Behav 30:1045–1050, 1988.
Murphy JM, Waller MB, Gatto GJ, McBride WJ, Lumeng L, Li T-K: Effects of fluoxetine on the intragastric self-administration of ethanol in the alcohol-preferring P line of rats. Alcohol 5:283–286, 1988.
Brown ZW, Amit Z: The effects of selective catecholamine depletions by 6-hydroxydopamine on ethanol preference in rats. Neurosci Lett 5:333–336, 1977.
Kiianmaa K, Fuxe K, Jonson G, Ahtee L: Evidence for involvement of central NA neurons in alcohol intake. Increased alcohol consumption after degeneration of the NA pathway in the cortex cerebri. Neurosci Lett 1:41–45, 1975.
Mason ST, Corcoran ME, Fibiger HC: Noradrenaline and ethanol intake in the rat. Neurosci Lett 12:137–142, 1979.
Hunt WA, Majchrowicz E: Alterations in the turnover of brain norepinephrine and dopamine in alcohol-dependent rats. J Neurochem 23:549–552, 1974.
Carlsson A, Lindquist M: Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25:437–440,1973.
Amit Z, Brown ZW: Actions of drugs of abuse on brain reward systems: a reconsideration with specific attention to alcohol. Pharmacol Biochem Behav 17:233–238, 1982.
Bustos G, Roth RH: Effect of acute ethanol treatment on transmitter synthesis and metabolism in central dopaminergic neurons. J Pharm Pharmacol 28:580–582, 1976.
Fadda F, Mosca E, Colombo G, Gessa GL: Effects of spontaneous ingestion of ethanol on brain dopamine metabolism. Life Sci 44:281–287, 1989.
Khatib SA, Murphy JM, McBride WJ: Biochemical evidence for activation of specific monoamine pathways by ethanol. Alcohol 5:295–299, 1988.
Carmichael FJ, Israel Y: Effects of ethanol on neurotransmitter release by rat cortical slices. J Pharmacol Exp Ther 193:824–834, 1975.
Holman RB, Snape BM: Effects of ethanol in vitro and in vivo on the release of endogenous catecholamines from specific regions of the rat brain. J Neurochem 44:357–363, 1985.
Korpi ER, Sinclair JD, Malminen O: Dopamine D2 receptor binding in striatal membranes of rats selected for differences in alcohol-related behaviors. Pharmacol Toxicol 61:94–97, 1987.
Liljeqvist S: Changes in the sensitivity of dopamine receptors in the nucleus accumbens and in the striatum induced by chronic ethanol administration. Acta Pharmacol Toxicol 43:19–28, 1978.
Lucchi L, Lupini M, Govoni S, Covelli V, Spano PF, Trabucchi M: Ethanol and dopaminergic systems. Pharmacol Biochem Behav 18(Suppl 1):379–382,1983.
DiChiara G, Imperato A: Preferential stimulation of dopamine release in mesolimbic systems: a common feature of drugs of abuse, in Sandier M, Feuerstein C, Scatton B (eds): Neurotransmitter Interactions in the Basal Ganglia. New York, Raven Press, 1988, p 171.
Koob GF, Vaccarino FJ, Amalric M, Swerdlow NR: Neural substrates for cocaine and opiate reinforcement, in Fischer S, Raskin A, Uhlenhuth EH (eds): Cocaine: Clinical and Biobehavioral Aspects. New York, Oxford University Press, 1987, p 80.
Siggins GR, Pittman QJ, French ED: Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: an intracellular study. Brain Res 414:22–34, 1987.
Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT: CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat. Psychopharmacology 103:227–232, 1991.
Cooper BR, Viik K, Ferris RM, White HL: Antagonism of the enhanced susceptibility to audiogenic seizures during alcohol withdrawal in the rat by gamma-aminobutyric acid (GABA) and GABA-mimetics. J Pharmacol Exp Ther 209:396–408, 1979.
Goldstein DB: Alcohol withdrawal reaction in mice: effects of drugs that modify neurotransmission. J Pharmacol Exp Ther 186:1–9, 1973.
Frye GD, McCown TJ, Breese GR: Differential sensitivity of ethanol withdrawal signs in the rat to gamma-aminobutyric acid (GABA) mimetics: blockade of audiogenic seizures but not forelimb tremors. J Pharmacol Exp Ther 226:720–723, 1983.
Lister RG, Karanian JW: RO15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal. Alcohol 4(5):409–411, 1987.
Patel GT, Lal H: Reduction brain GABA and in barbital narcosis during ethanol withdrawal. J Pharmacol Exp Ther 186:625–629, 1973.
Simler SJ, Clement L: Brain GABA turnover rates after spontaneous chronic ethanol intake and withdrawal indiscrete brain areas of C57 mice. J Neurochem 47:1942–1947, 1986.
Wixon HN, Hunt WA: Effect of acute and chronic ethanol treatment on GABA levels and on aminooxyacetic acid-induced GABA accumulation. Subst Alcohol Actions Misuse 1:481–491, 1980.
Rawat AK: Brain levels and turnover rates of presumptive neurotransmitters as influenced by administration and withdrawal of ethanol in mice. J Neurochem 22:915–922, 1974.
Little HJ: Mechanisms that may underlie the behavioral effects of ethanol. Prog Neurobiol 36:171–194, 1991.
Morrow AL, Suzdak PD, Karanian JW, Paul SM: Chronic ethanol administration alters gammaaminobutyric acid, pentobarbital and ethanol-mediated 36 C1-uptake in cerebral cortical synaptoneurosomes. J Pharmacol Exp Ther 246:158–164, 1988.
Aston-Jones G, Foote SL, Bloom FE: Low doses of ethanol disrupt sensory responses of brain noradrenergic neurones. Nature 296:857–860, 1982.
Rogers J, Siggins GR, Schulman JA, Bloom FE: Psychological correlates of ethanol intoxication, tolerance, and dependence in rat cerebellar Purkinje cells. Brain Res 196:183–198, 1980.
Koob GF, Bloom FE: Corticotropin releasing factor and behavior. Fed Proc 44:259–263, 1985.
Britton KT, Koob GF: Alcohol reverses the proconflict effect of corticotropin releasing factor. Regul Pept 16:315–320, 1987.
File SE, Baldwin HA, Hitchcott PK: Flumazenil but not nitrendipine reverses the increased anxiety during ethanol withdrawal in the rat. Psychopharmacology 98:252–264, 1989.
Mello NK: Animal models for the study of alcohol addiction. Psychoneuroendocrinology 1:347–357, 1976.
Weiss F, Koob GF: The neuropharmacology of ethanol self-administration, in Meyer RE, Koob GF, Lewis MJ, Baul SM (eds): Ethanol Reinforcement. Birkhauser, Boston, 1991, pp 125–162.
Koob GF, Swerdlow NR: Functional Output of the Mesolimbic Dopamine System. Annals of New York Academy of Sciences 537:216–227, 1988.
Givens BS, Breese, GR: Site-specific enhancement of gamma-aminobutyric acid-mediated inhibition of neural activity by ethanol in the rat medial septal area. J Pharmacol Exp Ther 254:528–538, 1990.
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Koob, G.F., Weiss, F. (1992). Neuropharmacology of Cocaine and Ethanol Dependence. In: Galanter, M. (eds) Recent Developments in Alcoholism. Recent Developments in Alcoholism, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1648-8_11
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