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Alcohol Withdrawal: Neuroadaptation and Sensitization

Published online by Cambridge University Press:  07 November 2014

Howard C. Becker
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Abstract

Repeated episodes of alcohol withdrawal may exacerbate the severity of future withdrawal occurrences. The progressive intensification of withdrawal symptoms may be manifested as a kindling-like mechanism. This sensitization process may reflect persistent perturbation in excitatory and inhibitory influences on brain function. Relapse is also thought to be affected by the kindling mechanism. Successive alcohol withdrawal experiences may also lead to neurologic damage and cognitive impairments. We review the research findings regarding the alcohol withdrawal kindling hypothesis and the implications of the kindling process on mechanisms of dependence, alcohol withdrawal treatment strategies, and the long-term repercussions of alcoholism.

Type
Feature Articles
Information
CNS Spectrums , Volume 4 , Issue 1: Neural Mechanisms of the Alcohol Abuse Cycle , January 1999 , pp. 38 - 40,57-65
Copyright
Copyright © Cambridge University Press 1999

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References

REFERENCES

1.Finn, DA, Crabbe, JC. Exploring alcohol withdrawal syndrome. Alcohol Health & Research World. 1997;21:149–156.Google ScholarPubMed
2.Anton, RF, Becker, HC. Pharmacotherapy and pathophysiology of alcohol withdrawal. In: Kranzler, HR, ed. The Pharmacology of Alcohol Abuse. Handbook of Experimental Pharmacology. Vol 114. Berlin, Germany: Springer-Verlag; 1995:315–367.Google Scholar
3.Yost, DA. Alcohol withdrawal syndrome. Am Fam Physician. 1996;54:657–664.Google Scholar
4.Metten, P, Crabbe, JC. Dependence and withdrawal. In: Deitrich, RA, Erwin, VG, eds. Pharmacological Effects of Alcohol on the Nervous System. New York, NY: CRC Press; 1996:269–290.Google Scholar
5.Victor, M, Adams, RD. The effect of alcohol on the nervous system. Res Publ Assoc Res Nerv Ment Dis. 1953;32:526–573.Google ScholarPubMed
6.Hillbom, ME. Alcohol withdrawal seizures and binge versus chronic drinking. In: Porter, RJ, Mattson, RH, Cramer, JA, Diamond, I, eds. Alcohol and Seizures: Basic Mechanisms and Clinical Concepts. Philadelphia, Pa: FA Davis Company; 1990:206–215.Google Scholar
7.Ballenger, JC, Post, RM. Kindling as a model for alcohol withdrawal syndromes. Br J Psychiatry. 1978;133:1–14.CrossRefGoogle Scholar
8.Becker, HC. Kindling in alcohol withdrawal. Alcohol Health & Research World. In press.Google Scholar
9.Becker, HC, Littleton, JM. The alcohol withdrawal “kindling” phenomenon: clinical and experimental findings. Alcohol Clin Exp Res. 1996;20:121A–124A.CrossRefGoogle ScholarPubMed
10.Goddard, GV, McIntyre, DC, Leech, DC. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol. 1969;25:295–330.Google Scholar
11.Gilbert, ME. Neurotoxicants and limbic kindling. In: Isaacson, RL, Jensen, KF, eds. The Vulnerable Brain and Environmental Risks. New York, NY: Plenum Press; 1992:173–192.CrossRefGoogle Scholar
12.Post, RM, Weiss, SRB, Pert, A. Implications of behavioral sensitization and kindling for stress-induced behavioral change. Adv Exp Med Biol. 1988;245:441–463.Google Scholar
13.McNamara, JO, Wada, JA. Kindling model. In: Engel, J, Pedley, TA, eds. Epilepsy: A Comprehensive Textbook. Philadelphia, Pa: Lippincott-Raven Publishers; 1997:419–425.Google Scholar
14.Brown, ME, Anton, RE, Malcolm, R, Ballenger, JC. Alcohol detoxification and withdrawal seizures: clinical support for a kindling hypothesis. Biol Psychiatry. 1988;23:507–514.Google Scholar
15.Lechtenberg, R, Worner, TM. Seizure risk with recurrent alcohol detoxification. Arch Neurol. 1990;47:535–538.CrossRefGoogle ScholarPubMed
16.Lechtenberg, R, Worner, TM. Relative kindling effects of detoxification and non-detoxification admissions in alcoholics. Alcohol Alcohol. 1991;26:221–225.Google Scholar
17.Lechtenberg, R, Worner, TM. Total ethanol consumption as a seizure risk factor in alcoholics. Acta Neurol Scand. 1992;85:90–94.Google Scholar
18.Moak, DH, Anton, RF. Alcohol-related seizures and the kindling effect of repeated detoxifications: the influence of cocaine. Alcohol Alcohol. 1996;31:135–143.CrossRefGoogle ScholarPubMed
19.Pieninkeroinen, IP, Telakivi, TM, Hillbom, ME. Outcome in subjects with alcohol-provoked seizures. Alcohol Clin Exp Res. 1992;16:955–959.CrossRefGoogle ScholarPubMed
20.Booth, BM, Blow, FC. The kindling hypothesis: further evidence from a US national study of alcoholic men. Alcohol Alcohol. 1993;28:593–598.Google ScholarPubMed
21.Pohorecky, LA, Roberts, P. Development of tolerance to and physical dependence on ethanol: daily versus repeated cycles treatment with ethanol. Alcohol Clin Exp Res. 1991;15:824–833.Google Scholar
22.Ulrichsen, J, Clemmesen, L, Hemmingsen, R. Convulsive behavior during alcohol dependence: discrimination between the role of intoxication and withdrawal. Psychopharmacology. 1992;107:97–102.Google Scholar
23.Becker, HC, Hale, RL. Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal “kindling.” Alcohol Clin Exp Res. 1993;17:94–98.Google Scholar
24.Becker, HC. Positive relationship between the number of prior ethanol withdrawal episodes and the severity of subsequent withdrawal seizures. Psychopharmacology. 1994;116:26–32.Google Scholar
25.Becker, HC, Diaz-Granados, JL, Weathersby, RT. Repeated ethanol withdrawal experience increases the severity and duration of subsequent withdrawal seizures in mice. Alcohol. 1997;14:319–326.Google Scholar
26.Becker, HC, Diaz-Granados, JL, Hale, RL. Exacerbation of ethanol withdrawal seizures in mice with a history of multiple withdrawal experience. Pharmacol Biochem Behav. 1997;57:179–183.CrossRefGoogle ScholarPubMed
27.Poldrugo, F, Snead, OC. Electroencephalographic and behavioral correlates in rats during repeated ethanol withdrawal syndromes. Psychopharmacology. 1984;83:140–146.Google Scholar
28.Veatch, LM, Gonzalez, LP. Repeated ethanol withdrawal produces site-dependent increases in EEG spiking. Alcohol Clin Exp Res. 1996;20:262–267.Google Scholar
29.Walker, DW, Zornetzer, SF. Alcohol withdrawal in mice: electroencephalographic and behavioral correlates. Electroencephalogr Clin Neurophysiol. 1974;36:233–243.CrossRefGoogle ScholarPubMed
30.Clemmesen, L, Ingvar, M, Hemmingsen, R, Bolwig, TG. Local cerebral glucose consumption during ethanol withdrawal in the rat: effects of single and multiple episodes and previous convulsive seizures. Brain Res. 1988;453:204–214.Google Scholar
31.Pinel, JPJ. Alcohol withdrawal seizures: implications of kindling. Pharmacol Biochem Behav. 1980;13:225–231.Google Scholar
32.Pinel, JPJ, Van Oot, PH, Mucha, RF. Intensification of the alcohol withdrawal syndrome by repeated brain stimulation. Nature. 1975;254:510–511.CrossRefGoogle ScholarPubMed
33.McCown, TJ, Breese, GR. Multiple withdrawals from chronic ethanol “kindles” inferior collicular seizure activity: evidence for kindling of seizures associated with alcoholism. Alcohol Clin Exp Res. 1990;14:394–399.Google Scholar
34.Veatch, LM, Gonzalez, LP. Chronic ethanol retards kindling of hippocampal area CA3. Neuroreport. 1997;8:1903–1906.Google Scholar
35.Deitrich, RA, Radcliffe, R, Erwin, VG. Pharmacological effects in the development of physiological tolerance and physical dependence. In: Begleiter, H, Kissin, B, eds. The Pharmacology of Alcohol and Alcohol Dependence. New York, NY: Oxford University Press; 1996:431–476.Google Scholar
36.Tabakoff, B, Hoffman, PL. Effect of alcohol on neurotransmitters and their receptors and enzymes. In: Begleiter, H, Kissin, B, eds. The Pharmacology of Alcohol and Alcohol Dependence. New York, NY: Oxford University Press, 1996:356–430.Google Scholar
37.Valenzuela, CF. Alcohol and neurotransmitter interactions. Alcohol Health & Research World. 1997;21:144–148.Google Scholar
38.Kokka, N, Sapp, DW, Taylor, AN, Olsen, RW. The kindling model of alcohol dependence: similar persistent reduction in seizure threshold to pentylenetetrazol in animals receiving chronic ethanol or chronic pentylenetetrazol. Alcohol Clin Exp Res. 1993;17:525–531.Google Scholar
39.McCown, TJ, Breese, GR. A potential contribution to ethanol withdrawal kindling: reduced GABA function in the inferior collicular cortex. Alcohol Clin Exp Res. 1993;17:1290–1294.Google Scholar
40.Kang, M, Spigelman, I, Sapp, DW, Olsen, RW. Persistent reduction of GABAA receptor-mediated inhibition in rat hippocampus after chronic intermittent ethanol treatment. Brain Res. 1996;709:221–228.CrossRefGoogle ScholarPubMed
41.Hu, XJ, Ticku, MK. Functional characterization of a kindling-like model of ethanol withdrawal in cortical cultured neurons after chronic intermittent ethanol exposure. Brain Res. 1997;767:228–234.CrossRefGoogle ScholarPubMed
42.Mahmoudi, M, Kang, MH, Tillakarante, N, Tobin, AJ, Olsen, RW. Chronic intermittent ethanol treatment in rats increases GABAA receptor alpha4-subunit expression: possible relevance to alcohol dependence. J Neurochem. 1997;68:2485–2492.Google Scholar
43.Chin, JH. Adenosine receptors in brain: neuromodulation and role in epilepsy. Ann Neurol. 1989;26:695–698.CrossRefGoogle ScholarPubMed
44.Dunwiddie, TV. The physiological role of adenosine in the central nervous system. Int Rev Neurobiol. 1985;27:63–139.Google Scholar
45.Dragunow, M. Purinergic mechanisms in epilepsy. Prog Neurobiol. 1988;31:85–108.Google Scholar
46.Jarvis, MF, Becker, HC. Single and repeated episodes of ethanol withdrawal increase adenosine α1, but not α2A, receptor density in mouse brain. Brain Res. 1998;786:80–88.CrossRefGoogle Scholar
47.Angelatou, F, Pagonopoulou, O, Kostopoulos, G. Changes in seizure latency correlate with alterations in α1 adenosine receptor binding during daily repeated pentylenete-trazol-induced convulsions in different mouse brain areas. Neurosci Lett. 1991;132:203–206.Google Scholar
48.Gleiter, CH, Deckert, J, Nutt, DJ, Marangos, PJ. Electroconvulsive shock (ECS) and the adenosine neuromodulatory system: effect of single or repeated ECS on the adenosine α1 and α2 receptors, adenylate cyclase and the adenosine uptake site. J Neurochem. 1989;52:641–646.Google Scholar
49.Choi, DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988;1:623–634.Google Scholar
50.Lovinger, DM. Excitotoxicity and alcohol-related brain damage. Alcohol Clin Exp Res. 1993;17:19–27.Google Scholar
51.Becker, HC, Veatch, LM, Diaz-Granados, JL. Repeated ethanol withdrawal experience selectively alters sensitivity to different chemoconvulsant drugs in mice. Psychopharmacology. 1998;139:145–153.Google Scholar
52.Little, HJ. The role of neuronal calcium channels in dependence on alcohol and other sedative/hypnotics. Pharmacol Ther. 1991;50:347–365.Google Scholar
53.Ulrichsen, J, Bech, B, Allerup, P, Hemmingsen, R. Diazepam prevents progression of kindled alcohol withdrawal behaviour. Psychopharmacology. 1995;121:451–460.Google Scholar
54.Mayo-Smith, MF, Bernard, D. Late-onset seizures in alcohol withdrawal. Alcohol Clin Exp Res. 1995;19:656–659.Google Scholar
55.Becker, HC, Walker, DJ, Reilly, SL, Studders, SL. Effect of benzodiazepine treatment of multiple ethanol withdrawals on later pentylenetetrazol (PTZ) seizure susceptibility. Alcohol Clin Exp Res. 1998;22:91A.Google Scholar
56.Ward, BO, Stephens, DN. Sensitization of withdrawal signs following repeated withdrawal from a benzodiazepine: differences between measures of anxiety and seizure sensitivity. Psychopharmacology. 1998;135:342–352.Google Scholar
57.Becker, HC, Studders, SL, Kelley, BM, Veatch, LM, Middaugh, LD. The subjective effects (discriminability) of ethanol is decreased during ethanol withdrawal in mice. Alcohol Clin Exp Res. 1998;22:49A.Google Scholar
58.Roberts, AJ, Cole, M, Koob, GF. Intra-amygdala muscimol decreases operant ethanol self-administration in dependent rats. Alcohol Clin Exp Res. 1996;20:1289–1298.Google Scholar
59.Weiss, F, Parsons, LH, Schulteis, G, et al.Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16:3474–3485.CrossRefGoogle ScholarPubMed
60.Koob, GF, Roberts, AJ, Schulteis, G, et al.Neurocircuitry targets in ethanol reward and dependence. Alcohol Clin Exp Res. 1998;22:3–9.Google Scholar
61.Davidson, M, Shanley, B, Wilce, P. Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study. Brain Res. 1995;674:91–96.Google Scholar
62.Davidson, MD, Wilce, P, Shanley, BC. Increased sensitivity of the hippocampus in ethanol-dependent rats to toxic effect of N-methyl-D-aspartic acid in vivo. Brain Res. 1993;606:5–9.Google Scholar
63.Lundqvist, C, Ailing, C, Knoth, R, Volk, B. Intermittent ethanol exposure of adult rats: hippocampal cell loss after one month of treatment. Alcohol Alcohol. 1995;30:737–748.Google Scholar
64.Lundqvist, C, Volk, B, Knoth, R, Ailing, C. Long-term effects of intermittent versus continuous ethanol exposure on hippocampal synapses of the rat. Acta Neuropathol. 1994;87:242–249.Google Scholar
65.Waltman, C, Wand, GS. Alterations in hypothalamic-pituitary-adrenal function by ethanol. In: Watson, RR, ed. Alcohol and Neurobiology: Brain Development and Hormone Regulation. Boca Raton, Fla: CRC Press; 1992:249–266.Google Scholar
66.Adinoff, B, Martin, PR, Bone, GHA, et al.Hypothalamic-pituitary-adrenal axis functioning and cerebrospinal fluid corticotropin releasing hormone and corticotropin levels in alcoholics after recent and long-term abstinence. Arch Gen Psychiatry. 1990;47:325–330.Google Scholar
67.Joëls, M, de Kloet, ER. Control of neuronal excitability by corticosteroid hormones. Trends Neurosci. 1992;15:25–30.Google Scholar
68.Roberts, AJ, Chu, HP, Crabbe, JC, Keith, LD. Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Alcohol Clin Exp Res. 1991;15:412–417.Google Scholar
69.Sapolsky, R. Glucocorticoids, hippocampal damage and the glutamatergic synapse. Prog Brain Res. 1990;86:13–23.Google Scholar
70.Sapolsky, RM, Uno, H, Rebert, CS, Finch, CE. Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci. 1991;10:2897–2902.Google Scholar
71.Hunt, WA. Are binge drinkers more at risk of developing brain damage? Alcohol. 1993;10:559–561.Google Scholar
72.Glenn, SW, Parsons, OA, Sinha, R, Stevens, L. The effects of repeated withdrawals from alcohol on the memory of male and female alcoholics. Alcohol Alcohol. 1988;23:337–342.Google Scholar
73.Bond, ND. Impairment of shuttlebox avoidance learning following repeated alcohol withdrawal episodes in rats. Pharmacol Biochem Behav. 1979;11:589–591.Google Scholar