Skip to main content
SpringerLink
Log in

Surgical and pharmacological suppression of glucocorticoids prevents the enhancement of morphine conditioned place preference by uncontrollable stress in rats

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

Abstract

Rationale

Stress and one of the physiological components of most stress responses, glucocorticoid hormones (CORT), are known to influence the rewarding effects of a number of drugs of abuse. We have previously shown that an acute uncontrollable stressor (inescapable shock, IS) potentiates the rewarding effects of morphine using conditioned place preference (CPP).

Objectives

The following experiments were conducted to determine the role of CORT in this process.

Methods

First, the CORT response to 3.0 mg/kg morphine was measured in male Sprague–Dawley rats 24 h following exposure to IS. Second, we determined the effect of adrenalectomy (ADX) on the IS-potentiated CPP to morphine. Finally, we used the temporary CORT synthesis inhibitors metyrapone and aminoglutethimide to determine the necessity of CORT rises during either IS or morphine administration on the potentiated CPP response.

Results

Prior IS significantly potentiated the CORT response to morphine. ADX significantly blocked the potentiated CPP to morphine produced by previous IS. However, CORT inhibition during IS had no effect on the IS potentiation of morphine CPP, whereas inhibition during morphine administration completely blocked this potentiation.

Conclusions

The results indicate that the CORT response to morphine is enhanced in rats that were previously exposed to an uncontrollable stressor, and that this response to the drug, not the stressor, is necessary for the stress-enhanced potentiation of morphine CPP.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Allolio B, Schulte HM, Deuss U, Kallabis D, Hamel E, Winkelman W (1987) Effect of oral morphine and naloxone on pituitary–adrenal response in man induced by human corticotropin-releasing hormone. Acta Endocrinol (Copenh) 114:509–514

    CAS  Google Scholar 

  • Amat J, Matus-Amat P, Watkins LR, Maier SF (1998a) Escapable and inescapable stress differentially alter extracellular levels of 5-HT in the basolateral amygdala of the rat. Brain Res 812:113–120

    Article  CAS  PubMed  Google Scholar 

  • Amat J, Matus-Amat P, Watkins LR, Maier SF (1998b) Escapable and inescapable stress differentially and selectively alter extracellular levels of 5-HT in the ventral hippocampus and dorsal periaqueductal gray of the rat. Brain Res 797:12–22

    Article  CAS  PubMed  Google Scholar 

  • Balfour DJ, Khullar AK, Longden A (1975) Effects of nicotine on plasma corticosterone and brain amines in stressed and unstressed rats. Pharmacol Biochem Behav 3:179–184

    Article  CAS  PubMed  Google Scholar 

  • Barrot M, Marinelli M, Abrous DN, Rouge-Pont F, Le Moal M, Piazza PV (2000) The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent. Eur J Neurosci 12:973–979

    Article  CAS  PubMed  Google Scholar 

  • Bland ST, Hargrave D, Pepin JL, Amat J, Watkins LR, Maier SF (2003) Stressor controllability modulates stress-induced dopamine and serotonin efflux and morphine-induced serotonin efflux in the medial prefrontal cortex. Neuropsychopharmacology 28:1589–1596

    Article  CAS  PubMed  Google Scholar 

  • Bland ST, Twining C, Schmid MJ, Der-Avakian A, Watkins LR, Maier SF (2004) Stress potentiation of morphine-induced dopamine efflux in the nucleus accumbens shell is dependent upon stressor uncontrollability and is mediated by the dorsal raphe nucleus. Neuroscience 126:705–715

    Article  CAS  PubMed  Google Scholar 

  • Broadbear JH, Winger G, Woods JH (1999) Cocaine-reinforced responding in rhesus monkeys: pharmacological attenuation of the hypothalamic–pituitary–adrenal axis response. J Pharmacol Exp Ther 290:1347–1355

    CAS  PubMed  Google Scholar 

  • Deroche V, Piazza PV, Casolini P, Maccari S, Le Moal M, Simon H (1992) Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion. Brain Res 598:343–348

    Article  CAS  PubMed  Google Scholar 

  • Deroche V, Piazza PV, Casolini P, Le Moal M, Simon H (1993) Sensitization to the psychomotor effects of amphetamine and morphine induced by food restriction depends on corticosterone secretion. Brain Res 611:352–356

    Article  CAS  PubMed  Google Scholar 

  • Deroche V, Piazza PV, Le Moal M, Simon H (1994) Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion. Brain Res 640:136–139

    Article  CAS  PubMed  Google Scholar 

  • Di Chiara G, Tanda G, Bassareo V, Pontieri F, Acquas E, Fenu S, Cadoni C, Carboni E (1999) Drug addiction as a disorder of associative learning. Role of nucleus accumbens shell/extended amygdala dopamine. Ann N Y Acad Sci 877:461–485

    PubMed  Google Scholar 

  • Ellis FW (1966) Effect of ethanol on plasma corticosterone levels. J Pharmacol Exp Ther 153:121–127

    CAS  PubMed  Google Scholar 

  • Erb S, Shaham Y, Stewart J (1998) The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats. J Neurosci 18:5529–5536

    CAS  PubMed  Google Scholar 

  • Goeders NE, Guerin GF (1996) Effects of surgical and pharmacological adrenalectomy on the initiation and maintenance of intravenous cocaine self-administration in rats. Brain Res 722:145–152

    Article  CAS  PubMed  Google Scholar 

  • Grahn RE, Will MJ, Hammack SE, Maswood S, McQueen MB, Watkins LR, Maier SF (1999) Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor. Brain Res 826:35–43

    Article  CAS  PubMed  Google Scholar 

  • Jacobson L, Akana SF, Cascio CS, Shinsako J, Dallman MF (1988) Circadian variations in plasma corticosterone permit normal termination of adrenocorticotropin responses to stress. Endocrinology 122:1343–1348

    CAS  PubMed  Google Scholar 

  • Jain MR, Patil PP, Subhedar N (1993) Direct action of metyrapone on brain: implication in feeding. Neuroreport 5:69–71

    CAS  PubMed  Google Scholar 

  • Johnson EO, Kamilaris TC, Chrousos GP, Gold PW (1992) Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis. Neurosci Biobehav Rev 16:115–130

    CAS  PubMed  Google Scholar 

  • Jolas T, Aghajanian GK (1997) Opioids suppress spontaneous and NMDA-induced inhibitory postsynaptic currents in the dorsal raphe nucleus of the rat in vitro. Brain Res 755:229–245

    Article  CAS  PubMed  Google Scholar 

  • de Kloet ER (2000) Stress in the brain. Eur J Pharmacol 405:187–198

    Article  PubMed  Google Scholar 

  • Knych ET, Eisenberg RM (1979) Effect of amphetamine on plasma corticosterone in the conscious rat. Neuroendocrinology 29:110–118

    CAS  PubMed  Google Scholar 

  • Koob GF (2000) Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci 909:170–185

    CAS  PubMed  Google Scholar 

  • Koob GF, Nestler EJ (1997) The neurobiology of drug addiction. J Neuropsychiatr Clin Neurosci 9:482–497

    CAS  PubMed  Google Scholar 

  • Kreek MJ (1996) Opiates, opioids and addiction. Mol Psychiatry 1:232–254

    CAS  PubMed  Google Scholar 

  • Le AD, Harding S, Juzytsch W, Watchus J, Shalev U, Shaham Y (2000) The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats. Psychopharmacology 150:317–324

    Article  PubMed  Google Scholar 

  • Lu L, Shepard JD, Scott Hall F, Shaham Y (2003) Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci Biobehav Rev 27:457–491

    Article  CAS  PubMed  Google Scholar 

  • Maier SF (1993) Learned helplessness, fear, and anxiety. Academic, London

    Google Scholar 

  • Maier SF, Seligman MEP (1976) Learned helplessness: theory and evidence. J Exp Psychol Gen 105:3–46

    Article  Google Scholar 

  • Maier SF, Ryan SM, Barksdale CM, Kalin NH (1986) Stressor controllability and the pituitary–adrenal system. Behav Neurosci 100:669–674

    Article  CAS  PubMed  Google Scholar 

  • Marinelli M, Piazza PV (2002) Interaction between glucocorticoid hormones, stress and psychostimulant drugs. Eur J Neurosci 16:387–394

    Article  PubMed  Google Scholar 

  • Maswood S, Barter JE, Watkins LR, Maier SF (1998) Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat. Brain Res 783:115–120

    Article  CAS  PubMed  Google Scholar 

  • Munck A, Guyre PM, Holbrook NJ (1984) Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev 5:25–44

    CAS  PubMed  Google Scholar 

  • Ohno Y, Nagamatsu K, Kawanishi T, Ikebuchi H, Terao T, Takanaka A (1988) Comparative evaluation of different pathways for the liver toxicity of morphine using freshly isolated hepatocytes. Biochem Pharmacol 37:2862–2863

    Article  CAS  PubMed  Google Scholar 

  • Pechnick RN (1993) Effects of opioids on the hypothalamo-pituitary–adrenal axis. Annu Rev Pharmacol Toxicol 33:353–382

    CAS  PubMed  Google Scholar 

  • Piazza PV, Le Moal M (1997) Glucocorticoids as a biological substrate of reward: physiological and pathophysiological implications. Brain Res Brain Res Rev 25:359–372

    Article  CAS  PubMed  Google Scholar 

  • Piazza PV, Rouge-Pont F, Deroche V, Maccari S, Simon H, Le Moal M (1996) Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission. Proc Natl Acad Sci USA 93:8716–8720

    Article  CAS  PubMed  Google Scholar 

  • Plotsky PM, Sawchenko PE (1987) Hypophysial–portal plasma levels, median eminence content, and immunohistochemical staining of corticotropin-releasing factor, arginine vasopressin, and oxytocin after pharmacological adrenalectomy. Endocrinology 120:1361–1369

    CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    Article  CAS  PubMed  Google Scholar 

  • Rotllant D, Ons S, Carrasco J, Armario A (2002) Evidence that metyrapone can act as a stressor: effect on pituitary–adrenal hormones, plasma glucose and brain c-fos induction. Eur J Neurosci 16:693–700

    Article  PubMed  Google Scholar 

  • Rouge-Pont F, Marinelli M, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion. J Neurosci 15:7189–7195

    CAS  PubMed  Google Scholar 

  • Saal D, Dong Y, Bonci A, Malenka RC (2003) Drugs of abuse and stress trigger a common synaptic adaptation in dopamine neurons. Neuron 37:577–582

    Article  CAS  PubMed  Google Scholar 

  • Sable-Amplis R, Agid R, Abadie D (1974) Reversal of the action of morphine on the secretory activity of the adrenal cortex. Biochem Pharmacol 23:2111–2118

    Article  CAS  PubMed  Google Scholar 

  • Shaham Y, Funk D, Erb S, Brown TJ, Walker CD, Stewart J (1997) Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 17:2605–2614

    CAS  PubMed  Google Scholar 

  • Shalev U, Marinelli M, Baumann MH, Piazza PV, Shaham Y (2003) The role of corticosterone in food deprivation-induced reinstatement of cocaine seeking in the rat. Psychopharmacology 168:170–176

    Article  CAS  PubMed  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359

    Article  CAS  PubMed  Google Scholar 

  • Spampinato U, Invernizzi R, Samanin R (1984) Evidence of serotonin involvement in the effect of morphine on dopamine metabolism in the rat nucleus accumbens but not in the striatum. Pharmacol Res Commun 16:519–523

    CAS  PubMed  Google Scholar 

  • Spencer RL, McEwen BS (1990) Adaptation of the hypothalamic–pituitary–adrenal axis to chronic ethanol stress. Neuroendocrinology 52:481–489

    CAS  PubMed  Google Scholar 

  • Suzuki T, Sugano Y, Funada M, Misawa M (1995) Adrenalectomy potentiates the morphine—but not cocaine-induced place preference in rats. Life Sci 56:PL339–PL344

    Article  CAS  PubMed  Google Scholar 

  • Ward AS, Collins ED, Haney M, Foltin RW, Fischman MW (1998) Ketoconazole attenuates the cortisol response but not the subjective effects of smoked cocaine in humans. Behav Pharmacol 9:577–586

    CAS  PubMed  Google Scholar 

  • Weiss JM, Goodman PA, Losito BA, Corrigan S, Charry JM, Bailey WH (1981) Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain. Brain Res Rev 3:167–205

    Article  CAS  Google Scholar 

  • Will MJ, Watkins LR, Maier SF (1998) Uncontrollable stress potentiates morphine’s rewarding properties. Pharmacol Biochem Behav 60:655–664

    Article  CAS  PubMed  Google Scholar 

  • Will MJ, Der-Avakian A, Bland ST, Grahn RE, Hammack SE, Sparks PD, Pepin JL, Watkins LR, Maier SF (2004) Electrolytic lesions and pharmacological inhibition of the dorsal raphe nucleus prevent stressor potentiation of morphine conditioned place preference in rats. Psychopharmacology 171:191–198

    Article  CAS  PubMed  Google Scholar 

  • Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Drs. Ruth E. Grahn, Sayamwong E. Hammack, and Kevin A. O’Connor for their excellent technical assistance. This research was supported by NIH grants DA13159, DA015642, and DA16004.

Author information

Authors and Affiliations

  1. Department of Psychology and Center for Neuroscience, University of Colorado, UCB 345, Boulder, CO, 80309-0345, USA

    Andre Der-Avakian, Sondra T. Bland, Kien T. Nguyen, Megan J. Schmid, Robert L. Spencer, Linda R. Watkins & Steven F. Maier

  2. Department of Psychiatry, Medical School, University of Wisconsin—Madison, Madison, WI, 53719, USA

    Matthew J. Will

  3. Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, Binghamton, NY, 13902-6000, USA

    Terrence Deak

Authors
  1. Andre Der-Avakian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew J. Will
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sondra T. Bland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Terrence Deak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kien T. Nguyen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Megan J. Schmid
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert L. Spencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Linda R. Watkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Steven F. Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andre Der-Avakian.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Der-Avakian, A., Will, M.J., Bland, S.T. et al. Surgical and pharmacological suppression of glucocorticoids prevents the enhancement of morphine conditioned place preference by uncontrollable stress in rats. Psychopharmacology 179, 409–417 (2005). https://doi.org/10.1007/s00213-004-2041-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-004-2041-1

Keywords

Search

Navigation