Effects of stress on alcohol drinking: a review of animal studies
- 1.7k Downloads
While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results.
This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking.
The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption.
A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking.
KeywordsStress Alcohol drinking Animal models
This work was supported by the NIH/NIAAA-sponsored Integrative Neuroscience Initiative on Alcoholism (INIAstress) Consortium (grant U01 AA014095).
Conflicts of interest
The authors do not have any conflicts of interest to report in connection with this manuscript.
- Adinoff B, Martin PR, Bone GH, Eckardt MJ, Roehrich L, George DT, Moss HB, Eskay R, Linnoila M, Gold PW (1990) 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 47:325–330PubMedGoogle Scholar
- Becker HC (1999) Alcohol withdrawal: neuroadaptation and sensitization. CNS Spectr 4:38–65Google Scholar
- Becker HC (2009) Alcohol dependence, withdrawal and relapse. Alcohol Res Health 31:348–361Google Scholar
- Bertholomey ML, Henderson AN, Badia-Elder NE, Stewart RB (2011) Neuropeptide Y (NPY)-induced reductions in alcohol intake during continuous access and following alcohol deprivation are not altered by restraint stress in alcohol-preferring (P) rats. Pharmacol Biochem Behav 97:453–461PubMedCrossRefGoogle Scholar
- Cappell H, Greeley J (1987) Alcohol and tension reduction: an update on research and theory. Guilford, New YorkGoogle Scholar
- Chen G, Cuzon Carlson VC, Wang J, Beck A, Heinz A, Ron D, Lovinger DM, Buck KJ (2011) Striatal involvement in human alcoholism and alcohol consumption, and withdrawal in animal models. Alcohol Clin Exp Res 35: doi: 10.1111/j.1530-0277.2011.01520.x
- Chester JA, de Paula BG, DeMaria A, Finegan A (2006) Different effects of stress on alcohol drinking behaviour in male and female mice selectively bred for high alcohol preference. Alcohol Alcsm 41:44–53Google Scholar
- Childs E, O’Connor S, de Wit H (2011) Bilateral interactions between acute psychosocial stress and acute intravenous alcohol in healthy men. Alcohol Clin Exp Res 35: doi: 10.1111/j.1530-0277.2011.01522.x
- Ciccocioppo R, Gehlert DR, Ryabinin A, Kaur S, Cippitelli A, Thorsell A, Le AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, McKinzie D, Morin M, Economidou D, Stopponi S, Cannella N, Braconi S, Kallupi M, de Guglielmo G, Massi M, George DT, Gilman J, Hersh J, Tauscher JT, Hunt SP, Hommer D, Heilig M (2009) Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol 43:491–498PubMedCrossRefGoogle Scholar
- Cox WM, Stainbrook GL (1977) Stress-induced alcohol consumption: a new paradigm. Alcohol Alcsm 12:23–29Google Scholar
- Darnaudery M, Louvart H, Defrance L, Leonhardt M, Morley-Fletcher S, Gruber SH, Galietta G, Mathe AA, Maccari S (2007) Impact of an intense stress on ethanol consumption in female rats characterized by their pre-stress preference: modulation by prenatal stress. Brain Res 1131:181–186PubMedCrossRefGoogle Scholar
- Davis MI (2008) Ethanol-BDNF interactions: still more questions than answers. Pharmacol Ther 118:36–57Google Scholar
- Fahlke C, Hansen S (1999) Effect of local intracerebral corticosterone implants on alcohol intake in the rat. Alcohol Alcsm 34:851–861Google Scholar
- Fahlke C, Hard E, Eriksson CJ, Engel JA, Hansen S (1995) Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat, and the effect of type I and type II corticosteroid receptor antagonists. Psychopharmacology (Berl) 117:216–224CrossRefGoogle Scholar
- Gehlert DR, Cippitelli A, Thorsell A, Le AD, Hipskind PA, Hamdouchi C, Lu J, Hembre EJ, Cramer J, Song M, McKinzie D, Morin M, Ciccocioppo R, Heilig M (2007) 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl- imidazo[1,2-b]pyridazine: a novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. J Neurosci 27:2718–2726PubMedCrossRefGoogle Scholar
- Haleem DJ (1996) Adaptation to repeated restraint stress in rats: failure of ethanol-treated rats to adapt in the stress schedule. Alcohol Alcsm 31:471–477Google Scholar
- Koolhaas JM, Bartolomussi A, Buwalda B, de Boer SF, Flugge G, Korte SM, Meerlo P, Murison R, Olivier B, Palanza P, Richter-Levin G, Sgoifo A, Steimer T, Stiedl O, van Dijk G, Wöhr M, Fuchs E (2011) Stress revisited: a critical evaluation of the stress concept. Neurosci Biobehav Rev 35:1291–1301PubMedCrossRefGoogle Scholar
- Kulkosky PJ, Zellner DA, Hyson RL, Riley AL (1980) Ethanol consumption of rats in individual, group, and colonial housing conditions. Physiol Psychol 8:56–60Google Scholar
- Le AD, Poulos CX, Harding S, Watchus J, Juzytsch W, Shaham Y (1999) Effects of naltrexone and fluoxetine on alcohol self-administration and reinstatement of alcohol seeking induced by priming injections of alcohol and exposure to stress. Neuropsychopharmacology 21:435–444PubMedCrossRefGoogle Scholar
- Lopez MF, Ralston LA, Becker HC (2006) Ethanol seeking and drinking behaviors: comparison of female and male C57BL/6J mice. Alcohol Clin Exp Res 30:188AGoogle Scholar
- Lopez MF, Anderson RI, Becker HC (2008) Repeated cycles of chronic intermittent ethanol exposure increase both self-administration and the reinforcing value of ethanol in C57BL/6J mice. Alcohol Clin Exp Res 32:163AGoogle Scholar
- Lopez MF, Griffin WC, Becker HC (2010) Ethanol intake, plasma corticosterone levels and brain region CRF levels in ethanol-dependent C57BL/6J mice. Alcohol Clin Exp Res 34:200AGoogle Scholar
- Matthews DB, Morrow AL, O'Buckley T, Flanigan TJ, Berry RB, Cook MN, Mittleman G, Goldowitz D, Tokunaga S, Silvers JM (2008) Acute mild footshock alters ethanol drinking and plasma corticosterone levels in C57BL/6J male mice, but not DBA/2J or A/J male mice. Alcohol 42:469–476PubMedCrossRefGoogle Scholar
- Mozhui K, Karlsson RM, Kash TL, Ihne J, Norcross M, Patel S, Farrell MR, Hill EE, Graybeal C, Martin KP, Camp M, Fitzgerald PJ, Ciobanu DC, Sprengel R, Mishina M, Wellman CL, Winder DG, Williams RW, Holmes A (2010) Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability. J Neurosci 30:5357–5367PubMedCrossRefGoogle Scholar
- Mutschler J, Bilbao A, von der Goltz C, Demiralay C, Jahn H, Wiedemann K, Spanagel R, Kiefer F (2010) Augmented stress-induced alcohol drinking and withdrawal in mice lacking functional natriuretic peptide-A receptors. Alcohol Alcsm 45:13–16Google Scholar
- Penev PD, Kolker DE, Zee PC, Turek FW (1998) Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease. Am J Physiol 275:2334–2337Google Scholar
- Pohorecky LA (1990) Interaction of ethanol and stress: research with experimental animals-an update. Alcohol Alcsm 25:263–276Google Scholar
- Rivier C (2000) Effects of alcohol on the neuroendocrine system. In: Noronha A et al (eds) Review of NIAAA's neuroscience and behavioral research portfolio: NIAAA Research Monograph No 34. National Institute on Alcohol Abuse and Alcoholism, Bethesda, pp 61–81Google Scholar
- Roberto M, Cruz MT, Gilpin NW, Sabino V, Schweitzer P, Bajo M, Cottone P, Madamba SG, Stouffer DG, Zorrilla EP, Koob GF, Siggins GR, Parsons LH (2010) Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol Psychiatry 67:831–839PubMedCrossRefGoogle Scholar
- Sandbak T, Murison R (2001) Behavioural responses to elevated plus-maze and defensive burying testing: effects on subsequent ethanol intake and effect of ethanol on retention of the burying response. Alcohol Alcsm 36:48–58Google Scholar
- Sinha R, Fox HC, Hong KI, Hansen J, Tuit K, Kreek MJ (2011) Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes. Arch Gen Psychiatry. doi: 10.1001/archgenpsychiatry.2011.49
- Volpicelli JR, Tiven J, Kimmel SC (1982) The relationship between tension reduction and ethanol consumption in rats. Physiol Psychol 10:114–116Google Scholar
- Von Wright JM, Pekanmaki L, Malin S (1971) Effects of conflict and stress on alcohol intake in rats. Q J Stud Alcohol 32:420–433Google Scholar
- Wand G (2000) Hypothalamic-pituitary-adrenal axis: changes and risk for alcoholism. In: Noronha A et al (eds) Review of NIAAA's neuroscience and behavioral research portfolio: NIAAA Research Monograph No 34. National Institute on Alcohol Abuse and Alcoholism, Bethesda, pp 397–415Google Scholar