Abstract
Physical dependence on ethanol was produced in four rhesus monkeys by IV ethanol administration every 8 h. Ethanol was administered on each occasion until the eyeblink reflex was lost. Evidence of physical dependence development, in the form of tremoring 8 h after an infusion, appeared on day 8 of chronic administration. Abrupt cessation of ethanol administration following 16 days of chronic administration was accompanied by moderate to severe tremoring, retching, vomiting, and one or more convulsions. Peak withdrawal occurred between 12 and 32 h after abrupt discontinuation of ethanol administration, and decreased over a period of 64–204 h. Ethanol dependence was then reinstated. Once every 3–4 days, ethanol was withheld for 16 h. Withdrawal signs were scored for the first 12 h of this period, and then a test dose of ethanol, phenobarbital, or baclofen was administered. Withdrawal or intoxication signs were scored over the next 4 h, at which time ethanol administration was resumed. Both ethanol and phenobarbital suppressed ethanol withdrawal sign in a dose-related manner, and produced dose-related intoxication. Baclofen was largely ineffective in reducing withdrawal-induced tremors, although it was capable of producing sedation of a different type than that produced by phenobarbital and ethanol.
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References
Blum K, Wallace JE, Schwerter HA, Eubanks JD (1976) Morphine suppression of ethanol withdrawal in mice. Experientia 32:79–82
Branchey M, Rauscher G, Kissin B (1971) Modifications in the response to alcohol following the establishment of physical dependence. Psychopharmacologia 22:314–322
Brogden RN, Speight TM, Avery GS (1974) Baclofen: A preliminary report of its pharmacological properties and therapentic efficacy in spasticity. Drugs 8 (1):1–14
Cooper BR, Viik K, Ferris RM, White HL (1979) Antagonism of the enhanced susceptibility to audiogenic seizures during alcohol withdrawal in the rat by γ-amino bytyric acid (GABA) and “GABA-mimetic” agents. J Pharmacol Exp Ther 209:396–403
Deneau GA, Yanagita AT, Seevers MH (1969) Self-administration of psychoactive substances by the monkey: A measure of psychological dependence. Psychopharmacologia 16:30–48
Ellis FW, Pick JF (1970) Experimentally induced ethanol dependence in rhesus monkeys. J Pharmacol Exp Ther 175:88–93
Essig CF, Jones BE, Lam RC (1969) The effect of pentobarbital on alcohol withdrawal in dogs. Arch Neurol (Chicago) 20:554–558
Falk JL, Samson HH, Winger G (1972) Behavioral maintenance of high blood ethanol and physical dependence in the rat. Science (Washington) 177:811–813
Golbert TM, Sanz CJ, Rose HD, Leitschuh TH (1967) Comparative evaluation of treatments of alcohol withdrawal syndromes. J Amer Med Assoc 201:99–102
Goldstein DB (1972) An animal model for testing effects of drugs on alcohol withdrawal reactions. J Pharmacol Exp Ther 183:14–22
Goldstein DB (1973) An animal model for testing effects of drugs that modify neurotransmission. J Pharmacol Exp Ther 186:1–9
Goldstein DB (1974) Rates of onset and decay of alcohol physical dependence in mice. J Pharmacol Exp Ther 190:377–383
Goldstein DB (1979) Sodium bromide and sodium valproate: Effective suppressants of ethanol withdrawal reactions in mice. J Pharmacol Exp Ther 208:223–227
Himmelsbach CK, Andrews HL (1943) Studies on modification of the morphine abstinence syndrome by drugs. J Pharmacol Exp Ther 77:417–23
Hudgson P, Weightman D (1971) Baclofen in the treatment of spasticity. Br Med J 4:15–17
Isbell H, Fraser HF, Wikler A, Belleville RE, Eisenman AJ (1955) An experimental study of the etiology of “rum fits” and delirium tremens. Q J Stud Alcohol 16:1–33
Kalant H, LeBlane AE, Gibbins RJ (1971) Tolerance to, and dependence on, some non-opiate psychotropic drugs. Pharmacol Rev 23:135–191
Majchrowicz E, Hunt WA, Piantadosi C (1976) Suppression by 1,3-butanediol of the ethanol withdrawal syndrome in rats. Science (Washington) 194:1181–1182
Mendelson JH, La Don J (1964) Experimentally induced chronic intoxication and withdrawal in alcoholics. Q J Stud Alcohol Suppl 2:14–39
Naik SR, Guidotti A, Costa E (1976) Central GABA receptor agonists: Comparison of muscimol and baclofen. Neuropharmacology 15 (8):479–484
Noble EP, Gillies R, Vigran R, Mandel P (1976) The modification of the ethanol withdrawal syndrome in rates by di-n-propylacetate. Psychopharmacologia 46:127–131
Pedersen E, Arlien-Soborg P, Grynderup V, Henriksen O (1970) GABA derivative in spasticity. Acta Neurol Scand 46:257–266
Pieper WA, Skeen MJ (1972) Induction of physical dependence on ethanol in rhesus monkeys using oral acceptance technique. Life Sci 11:989–997
Pieper WA, Skeen MJ, McClure HM, Bourne PG (1972) The chimpanzee as an animal model for investigating alcoholism. Science (Washington) 176:71–73
Robson RE, Saelens JK, Wilson D (1977) Suppression of morphine withdrawal symptoms by baclofen (BF) (Lioresal®). Fed Proc 36:1025
Sprague GL, Craigmill AL (1976) Control of ethanol withdrawal symptoms in mice by phenytoin. Res Commn Chem Pathol Pharmacol 15:721–734
Victor M, Adams RD (1953) The effect of alcohol on the nervous system. Res Publ Assoc Res Nerv Ment Dis 32:526–273
Waddington JL, Cross AJ (1979) Baclofen and muscimol: Behavioral and neurochemical sequelae of unilateral intranigral administration and effects on 3H-GABA receptor binding. Arch Pharmacol 306:275–280
Winger GD, Woods JH (1973) The reinforcing properties of ethanol in the rhesus monkey. I. Initiation, maintenance and termination of intravenous ethanol-reinforced responding. Ann N Y Acad Sci 215:162–175
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Tarika, J.S., Winger, G. The effects of ethanol, phenobarbital, and baclofen on ethanol withdrawal in the rhesus monkey. Psychopharmacology 70, 201–208 (1980). https://doi.org/10.1007/BF00435315
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DOI: https://doi.org/10.1007/BF00435315