Skip to main content
Log in

Social defeat increases alcohol preference of C57BL/10 strain mice; effect prevented by a CCKB antagonist

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

In humans, social stress over long and short term can increase alcohol consumption, but the mechanisms involved are not understood.

Objectives

This study was conducted to examine the effects of social defeat, using the resident/intruder paradigm, on the alcohol preference of “low alcohol drinking” individuals in a colony of C57BL/10 strain mice and the effects of two anxiolytic drugs.

Methods

Alcohol preference, in a two-bottle choice (8% v/v alcohol or water), was measured, in separate experiments, after either a single experience of social defeat by a resident male mouse, five consecutive daily defeat experiences or one experience per week for 4 weeks. Comparison was made with effects of repeated social defeat on the preference for dilute sucrose. In addition, the actions of the CCKB receptor antagonist, CAM1028, and of diazepam were examined on the effects of repeated defeat experiences.

Results

Five consecutive daily defeat experiences had a slow onset effect in increasing alcohol preference and consumption, compared with five daily exposures to a novel environment. A single defeat, or one defeat per week, did not significantly alter alcohol preference or intake. There were no effects of five daily defeat experiences on sucrose preference or consumption. The effect of repeated defeats on alcohol preference was significantly decreased by administration of the CCKB receptor antagonist, CAM1028, prior to each experience, but not by corresponding administration of diazepam.

Conclusion

The results show that social stress increases alcohol intake in low alcohol preference C57BL/10 mice and suggest that CCK transmission may be involved in this effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Adamec R (1997) Transmitter systems involved in neural plasticity underlying increased anxiety and defence—implications for understanding anxiety following traumatic stress. Neurosci Biobehav Rev 21:755–765

    Article  PubMed  CAS  Google Scholar 

  • Adinoff B, Martin PR, Bone GH, Eckhardt MJ, Roerich 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 47:325–330

    PubMed  CAS  Google Scholar 

  • Bhatnagar S, Viau V, Chu A, Soriano L, Meijer OC, Dallman MF (2000) A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic–pituitary–adrenal function. J Neurosci 20:5564–5573

    PubMed  CAS  Google Scholar 

  • Blanchard DC, Sakai RR, McEwan B, Weiss SM, Blanchard RJ (1993) Subordination stress: behavioral, brain and neuroendocrine correlates. Behav Brain Res 58:113–121

    Article  PubMed  CAS  Google Scholar 

  • Brown SA, Vik PW, McQuaid JR, Patterson TL, Irwin MR, Grant I (1990) Severity of psychosocial stress and outcome of alcoholism treatment. J Abnorm Psychol 99:344–348

    Article  PubMed  CAS  Google Scholar 

  • Buwalda B, de Boer SF, Schmidt ED, Felszeghy K, Nyakas C, Sgoifo A, Van der Vegt BJ, Tilders FJ, Bohus B, Koolhaas JM (1999) Long lasting dexamethasone suppression of hypothalamic–pituitary–adrenocortical activation following peripheral CRF challenge in socially defeated rats. J Neuroendocrinol 11:513–520

    Article  PubMed  CAS  Google Scholar 

  • Buwalda B, Felszeghy K, Horvath KM, Nyakas C, de Boer SF, Bohus B, Koolhaas JM (2001) Temporal and spatial dynamics of corticosterone down-regulation in rat brain following social defeat. Physiol Behav 72:349–354

    Article  PubMed  CAS  Google Scholar 

  • Crespi F, Corsi M, England T, Ratti E, Tris, DG, Gaviraghi G (1997) Spontaneous preference for ethanol in naive rats is influenced by cholecystokininA receptor antagonism. Alcohol 14:327–332

    Article  PubMed  CAS  Google Scholar 

  • Crum RM, Muntarne C, Eaton WW, Anthony JC (1995) Occupational stress and the risk of alcohol abuse and dependence. Alcohol Clin Exp Res 19:647–655

    Article  PubMed  CAS  Google Scholar 

  • Dawson GR, Rupniak NMJ, Iversen SD, Curnow R, Tye S, Stanhope KJ, Tricklebank MD (1995) Lack of effect of CCKB receptor antagonists in ethological and conditioned animal screens for anxiolytic drugs. Psychopharmacology 121:109–117

    Article  PubMed  CAS  Google Scholar 

  • Ehrenreich H, Schuck N, Stender N, Pitz J, Gefeller O, Schilling L, Poser W, Kaw S (1997) Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol Clin Exp Res 21:1285–1293

    PubMed  CAS  Google Scholar 

  • Ellison G (1987) Stress and alcohol intake; a sociopharmacological approach. Physiol Behav 40:387–392

    Article  PubMed  CAS  Google Scholar 

  • Fahlke C, Hanson S (1999) Effect of local intracerebral corticosterone implants on alcohol consumption. Soc Neurosci Abstr 25:440.13

    Google Scholar 

  • Fahlke C, Engel JA, Eriksson CPJ, Har E, Soderpalm B (1994a) Involvement of corticosterone in the modulation of ethanol consumption in the rat. Alcohol 11:195–202

    Article  PubMed  CAS  Google Scholar 

  • Fahlke C, Hard E, Thomasson R, Engel JA, Hansen S (1994b) Metyrapone-induced suppression of corticosterone synthesis reduces ethanol consumption in high-preferring rats. Pharmacol Biochem Behav 48:977–981

    Article  PubMed  CAS  Google Scholar 

  • Fahlke C, Hard E, Eriksson CPJ, Engel JA, Hansen S (1995) Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomised rat, and the effect of type I and type II corticosteroid receptor antagonists. Psychopharmacology 117:216–224

    Article  PubMed  CAS  Google Scholar 

  • Farren CK, Clare AW, Dinan TG (1995) Basal serum cortisol and dexamethasone-induced growth hormone release in the alcohol dependence syndrome. Hum Psychopharmacol 10:207–213

    Article  Google Scholar 

  • Fidler TL, LoLordo VM (1996) Failure to find postshock increases in ethanol preference. Alcohol Clin Exp Res 20:110–121

    Article  PubMed  CAS  Google Scholar 

  • Funk D, Vohra S, Le AD (2004) Influence of stressors on the rewarding effects of alcohol in Wistar rats: studies with alcohol deprivation and place conditioning. Psychopharmacology 176:82–87

    Article  PubMed  CAS  Google Scholar 

  • Gorman DM, Brown GW (1992) Recent developments in life-event research and their relevance for the study of addictions. Br J Addict 87:837–849

    Article  PubMed  CAS  Google Scholar 

  • Haller J, Kiem DT, Makara GB (1996) The physiology of social conflict in rats: what is particularly stressful? Behav Neurosci 110:353–359

    Article  PubMed  CAS  Google Scholar 

  • Harper DG, Tornatzki W, Miczek KA (1996) Stress-induced disorganisation of circadian and ultradian rhythms: comparison of effects of surgery and social stress. Physiol Behav 59:409–419

    Article  PubMed  CAS  Google Scholar 

  • Harro J, Wahlström G, Oreland L (1994) Cholecystokinin receptor binding after long-term ethanol treatment in rats. Alcohol Alcohol 29:575–581

    PubMed  CAS  Google Scholar 

  • Harro J, Lofberg C, Rehfield JF, Oreland L (1996) Cholecystokinin peptides and receptors in the rat brain during stress. Naunyn-Schmiedebergs Arch Pharmakol 354:59–66

    Article  CAS  Google Scholar 

  • Hughes J, Boden P, Costall B, Domeney AM, Kelly EM, Horwell D, Hunter JC, Pinnock RD, Woodruff GN (1990) Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A 87:6728–6732

    Article  PubMed  CAS  Google Scholar 

  • Keeney AJ, Hogg S (1999) Behavioural consequences of repeated social defeat in the mouse: preliminary evaluation of a potential animal model of depression. Behav Pharmacol 10:753–764

    Article  PubMed  CAS  Google Scholar 

  • Koolhaas JM, Meerlo P, de Boer SF, Strubbe JH, Bohus B (1997) The temporal dynamics of the stress response. Neurosci Biobehav Rev 21:775–782

    Article  PubMed  CAS  Google Scholar 

  • Kulkosky PJ, Claybourne YJ, Sandova SL (1993) Cholecystokinin and bombesin inhibit ethanol and food intake in rats selectively bred for ethanol sensitivity. Alcohol Clin Exp Res 17:545–551

    Article  PubMed  CAS  Google Scholar 

  • Little HJ, Butterworth AR, O'Callaghan MJ, Wilson J, Cole J, Watson WP (1999) C57 strain mice with low alcohol preference; preference increased by saline injections. Psychopharmacology 147:182–189

    Article  PubMed  CAS  Google Scholar 

  • Martinez M, Phillips PJ, Herbert J (1998) Adaptation in patterns of c-fos expression in the brain associated with exposure to either single or repeated social stress in male rats. Eur J Neurosci 10:20–33

    Article  PubMed  CAS  Google Scholar 

  • Meerlo P, De Boer SF, Koolhaas JM, Daan S, Van Den Hoofdakker RH (1996) Changes in daily rhythms of body temperature and activity after a single social defeat in rats. Physiol Behav 59:735–739

    Article  PubMed  CAS  Google Scholar 

  • Nash JF, Maickel RP (1985) Stress-induced consumption of ethanol by rats. Life Sci 37:757–765

    Article  PubMed  CAS  Google Scholar 

  • Ng Cheong Ton MJ, Brown Z, Michalakeas A, Amit Z (1983) Stress induced suppression of maintenance but not of acquisition of ethanol consumption in rats. Pharmacol Biochem Behav 18:141–144

    Article  PubMed  CAS  Google Scholar 

  • O'Callaghan MJ, Croft AP, Little HJ (2002a) Effects of intraperitoneal injections of saline on alcohol and sucrose consumption of C57/BL10 mice. Psychopharmacology 160:206–212

    Article  PubMed  CAS  Google Scholar 

  • O'Callaghan MJ, Croft AP, Watson WP, Brooks SP, Little HJ (2002b) Low alcohol preference among the ‘high alcohol preference’ C57 strain of mice; factors affecting preference. Pharmacol Biochem Behav 72:475–481

    Article  PubMed  Google Scholar 

  • Philipp E, Wilckens T, Friess E, Platte P, Pirke KM (1992) Cholecystokinin, gastrin and stress hormone responses in marathon runners. Peptides 13:125–128

    Article  PubMed  CAS  Google Scholar 

  • Rockman GE, Hall A, Hong J, Glavin GB (1987) Unpredictable cold-immobilisation stress effects of voluntary ethanol consumption in rats. Life Sci 40:1245–1251

    Article  PubMed  CAS  Google Scholar 

  • Siegel RA, Duker E-M, Fuchs E, Pahnk U, Wuttke W (1984) Responsiveness of mesolimbic, mesocortical, septal and hippocampal cholecystokinin and substance P neuronal systems to stress in male rat. Neurochem Int 6:783–789

    Article  CAS  Google Scholar 

  • Singh L, Field MJ, Hughes J, Menzies R, Oles RJ, Vass CA, Woodruff GN (1991) The behavioral properties of CI988, a selective cholecystokininB receptor antagonist. Br J Pharmacol 104:239–245

    PubMed  CAS  Google Scholar 

  • Tidey JW, Miczek KA (1996) Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study. Brain Res 721:140–149

    Article  PubMed  CAS  Google Scholar 

  • Tornatzki W, Miczek KA (1993) Long term impairment of autonomic circadian rhythms after brief intermittent social stress. Physiol Behav 53:983–993

    Article  PubMed  Google Scholar 

  • Toth P, Shaw C, Perlanski E, Grupp LA (1990) Cholecystokinin octapeptide reduces ethanol intake in food- and water-sated rats. Pharmacol Biochem Behav 35:493–495

    Article  PubMed  CAS  Google Scholar 

  • van Erp AMM, Miczek KA (2001) Persistent suppression of ethanol self-administration by brief social stress in rats and increased startle response as index of withdrawal. Physiol Behav 73:301–311

    Article  PubMed  Google Scholar 

  • van Erp AMM, Tachi N, Miczek KA (2001) Short or continuous social stress: suppression of continuously available ethanol intake in subordinate rats. Behav Pharmacol 12:335–342

    PubMed  Google Scholar 

  • Vescovi PP, DiGennaro C, Coiro V (1997) Hormonal (ACTH, cortisol, β-endorphin and met-enkephalin) and cardiovascular responses to hyperthermic stress in chronic alcoholics. Alcohol Clin Exp Res 21:1195–1198

    PubMed  CAS  Google Scholar 

  • Volpicelli JR, Ulm RR, Hopson N (1986) The bidirectional effects of shock on alcohol preference in rats. Alcohol Clin Exp Res 14:913–916

    Article  Google Scholar 

  • Wilson J, Watson WP, Little HJ (1998) CCKB antagonists protect against anxiety-related behavior produced by ethanol withdrawal measured using the elevated plus maze. Psychopharmacology 137:120–131

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank NIAAA for financial support (grant no RO1 AA14262 to HJL).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. J. Little.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Croft, A.P., Brooks, S.P., Cole, J. et al. Social defeat increases alcohol preference of C57BL/10 strain mice; effect prevented by a CCKB antagonist. Psychopharmacology 183, 163–170 (2005). https://doi.org/10.1007/s00213-005-0165-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0165-6

Keywords

Navigation