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Gender differences in cardiovascular and corticoadrenal response to stress and drug cues in cocaine dependent individuals

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Abstract

Rationale

Extensive research suggests that gender may affect neuroendocrine and cardiovascular arousal mechanisms underlying biological responses to stress.

Objective

To examine the impact of gender on response to stress and to drug-cue exposure in treatment-seeking cocaine abusers.

Methods

Fifty recently abstinent cocaine dependent individuals (25F/25M), who were matched on cocaine use history, were exposed to a brief guided-imagery procedure that involved imagining a recent personal stressful situation, a personal drug-related situation and neutral-relaxing situation, one imagery per session, presented in random order. Subjective craving and anxiety, cardiovascular measures and plasma adrenocorticotrophic hormone (ACTH), cortisol and prolactin were assessed.

Results

Males showed significantly higher levels of ACTH, cortisol, and SBP, both at baseline and following all three imagery conditions. Females showed significantly higher basal heart rate and prolactin, although no gender differences were observed following imagery. No gender differences were seen in subjective anxiety or cocaine craving.

Conclusions

Results indicate significant gender differences in baseline sensitivity and subsequent variations in hypothalamus–pituitary–adrenal (HPA) and cardiovascular response to imagery challenge. Such gender-specific responses could have implications for the development of pharmacological treatments that address stress and drug-cue-related relapse in cocaine-abusing individuals.

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References

  • Adinoff B, Risher-Flowers D, De Jong J, Ravitz B, Bone GH, Nutt DJ, Roehrich L, Martin PR, Linnoila M (1991) Disturbances of hypothalamic–pituitary–adrenal axis functioning during ethanol withdrawal in six men. Am J Psychiatry 148(8):1023–1025

    PubMed  Google Scholar 

  • Allen MT, Stoney CM, Owens JF, Matthews KA (1993) Hemodynamic adjustments to laboratory stress: the influence of gender and personality. Psychosom Med 55:505–517

    PubMed  Google Scholar 

  • Anthenelli RM, Maxwell RA, Geracioti TD Jr, Hauger R (2001) Stress hormone dysregulation at rest and after serotonergic stimulation among alcohol-dependent men with extended abstinence and controls. Alcohol Clin Exp Res 25(5):692–703

    Article  PubMed  Google Scholar 

  • Atkinson HC, Waddell BJ (1997) Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. Endocrinology 138:3842–3848

    Article  PubMed  Google Scholar 

  • Avants SK, Margolin A, Kosten TR, Cooney NL (1995) Differences between responders and nonresponders to cocaine cues in the laboratory. Addict Behav 20:215–224

    Article  PubMed  Google Scholar 

  • Back SE, Brady KT, Jackson JL, Salstrom S, Zinzow H (2005) Gender differences in stress reactivity among cocaine-dependent individuals. Psychopharmacology (Berl) 180:169–176

    Article  Google Scholar 

  • Born J, Ditschuneit I, Schreiber M, Dodt C, Fehm HL (1995) Effects of age and gender on pituitary-adrenocortical responsiveness in humans. Eur J Endocrinol 132:705–711

    PubMed  Google Scholar 

  • Brunova J (2004) Endocrine diseases and diabetes. Cas Lek Cesk 143:507–511

    PubMed  Google Scholar 

  • Campbell UC, Morgan AD, Carroll ME (2002) Sex differences in the effects of baclofen on the acquisition of intravenous cocaine self-administration in rats. Drug Alcohol Depend 66:61–69

    Article  PubMed  Google Scholar 

  • Carroll KM, Fenton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ (2004) Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial. Arch Gen Psychiatry 61:264–272

    Article  PubMed  Google Scholar 

  • Cohen S, Kessler RC, Gordon, LU (1995) Strategies for measuring stress in studies of psychiatric and physical disorders. In: Cohen S, Kessler RC, Gordon LU (eds) Measuring stress: a guide for health and social scientists. Oxford University Press, New York, pp 3–26

    Google Scholar 

  • Dinan TG, Scott LV (2005) Anatomy of melancholia: focus on hypothalamic pituitary adrenal axis overactivity and the role of vasopressin. J Anat 207(3):259–264

    Article  PubMed  Google Scholar 

  • Dorn LD, Burgess ES, Susman EJ, von Eye A, DeBellis MD, Gold PW, Chrousos GP (1996) Response to oCRH in depressed and nondepressed adolescents: does gender make a difference? J Am Acad Child Adolesc Psychiatry 35:764–773

    Article  PubMed  Google Scholar 

  • Earle TL, Linden W, Weinberg J (1999) Differential effects of harassment on cardiovascular and salivary cortisol stress reactivity and recovery in women and men. J Psychosom Res 46:125–141

    Article  PubMed  Google Scholar 

  • Elman I, Karlsgodt KH, Gastfriend DR (2001) Gender differences in cocaine craving among non-treatment-seeking individuals with cocaine dependence. Am J Drug Alcohol Abuse 27:193–202

    Article  PubMed  Google Scholar 

  • Everitt B, Rabe-Hesketh S (2001) Analyzing medical data using s-plus. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Frankenhaeuser M, von Wright MR, Collins A, von Wright J, Sedvall G, Swahn CG (1978) Sex differences in psychoneuroendocrine reactions to examination stress. Psychosom Med 40:334–343

    PubMed  Google Scholar 

  • Goeders NE (2002) The HPA axis and cocaine reinforcement. Psychoneuroendocrinology 27:13–34

    Article  PubMed  Google Scholar 

  • Gold SM, Dziobek I, Rogers K, Bayoumy A, McHugh PF, Convit A (2005) Hypertension and hypothalamo–pituitary–adrenal axis hyperactivity affect frontal lobe integrity. J Clin Endocrinol Metab 90(6):3262–3267

    Article  PubMed  Google Scholar 

  • Handa RJ, Burgess LH, Kerr JE, O’Keefe JA (1994) Gonadal steroid hormone receptors and sex differences in the hypothalamo–pituitary–adrenal axis. Horm Behav 28:464–476

    Article  PubMed  Google Scholar 

  • Horrocks PM, Jones AF, Ratcliffe WA, Holder G, White A, Holder R, Ratcliffe JG, London DR (1990) Patterns of ACTH and cortisol pulsatility over twenty-four hours in normal males and females. Clin Endocrinol (Oxf) 32:127–134

    Google Scholar 

  • Jezova D, Jurankova E, Vigas M (1995) Glutamate neurotransmission, stress and hormone secretion. Bratisl Lek Listy 96:588–596

    PubMed  Google Scholar 

  • Kirschbaum C, Wust S, Hellhammer D (1992) Consistent sex differences in cortisol responses to psychological stress. Psychosom Med 54:648–657

    PubMed  Google Scholar 

  • Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH (1999) Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus–pituitary–adrenal axis. Psychosom Med 61:154–162

    PubMed  Google Scholar 

  • Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Davis SM, Harrison WM, Keller MB (2000) Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 157:1445–1452

    Article  PubMed  Google Scholar 

  • Kranzler HR, Wallington DJ (1992) Serum prolactin level, craving, and early discharge from treatment in cocaine-dependent patients. Am J Drug Alcohol Abuse 18:187–195

    PubMed  Google Scholar 

  • Kudielka BM, Hellhammer J, Hellhammer DH, Wolf OT, Pirke KM, Varadi E, Pilz J, Kirschbaum C (1998) Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment. J Clin Endocrinol Metab 83:1756–1761

    Article  PubMed  Google Scholar 

  • Kudielka BM, Kirschbaum C (2005) Sex differences in HPA axis responses to stress: a review. Biol Psychol 69:113–132

    Article  PubMed  Google Scholar 

  • Laird NM, Ware JH (1982) Random-effects models for longitudinal data. Biometrics 38:963–974

    PubMed  Google Scholar 

  • Littell R, Milliken G, Strout W, Wolfinger R (1996) SAS system for mixed models. SAS Institute, Cary, North Carolina

    Google Scholar 

  • Lovallo WR, Dickensheets SL, Myers DA, Thomas TL, Nixon SJ (2000) Blunted stress cortisol response in abstinent alcoholic and polysubstance-abusing men. Alcohol Clin Exp Res 24(5):651–658

    Article  PubMed  Google Scholar 

  • Luisi S, Tonetti A, Bernardi F, Casarosa E, Florio P, Monteleone P, Gemignani R, Petraglia F, Luisi M, Genazzani AR (1998) Effect of acute corticotropin releasing factor on pituitary-adrenocortical responsiveness in elderly women and men. J Endocrinol Investig 21:449–453

    Google Scholar 

  • Lynch WJ, Carroll ME (2000) Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacology (Berl) 148:196–200

    Article  Google Scholar 

  • Matthews KA, Gump BB, Owens JF (2001) Chronic stress influences cardiovascular and neuroendocrine responses during acute stress and recovery, especially in men. Health Psychol 20:403–410

    Article  PubMed  Google Scholar 

  • McCance-Katz EF, Carroll KM, Rounsaville BJ (1999) Gender differences in treatment-seeking cocaine abusers-implications for treatment and prognosis. Am J Addict 8:300–311

    Article  PubMed  Google Scholar 

  • McDougle CJ, Price LH, Palumbo JM, Kosten TR, Heninger GR, Kleber HD (1992) Dopaminergic responsivity during cocaine abstinence: a pilot study. Psychiatry Res 43:77–85

    Article  PubMed  Google Scholar 

  • McMurray RW (2001) Estrogen, prolactin, and autoimmunity: actions and interactions. Int Immunopharmacol 1:995–1008

    Article  PubMed  Google Scholar 

  • Mercer D, Carpenter G, Daley D, Patterson C, Volpicelli J (1994) Group drug counseling manual. University of Pennsylvania

  • Milani RM, Parrott AC, Turner JJ, Fox HC (2004) Gender differences in self-reported anxiety, depression, and somatization among ecstasy/MDMA polydrug users, alcohol/tobacco users, and nondrug users. Addict Behav 29(5):965–971

    Article  PubMed  Google Scholar 

  • Nich C, McCance-Katz EF, Petrakis IL, Cubells JF, Rounsaville BJ, Carroll KM (2004) Sex differences in cocaine-dependent individuals’ response to disulfiram treatment. Addict Behav 29:1123–1128

    Article  PubMed  Google Scholar 

  • Pariante CM (2003) Depression, stress and the adrenal axis. J Neuroendocrinol 15:811–812

    PubMed  Google Scholar 

  • Patkar AA, Hill KP, Sterling RC, Gottheil E, Berrettini WH, Weinstein SP (2002) Serum prolactin and response to treatment among cocaine-dependent individuals. Addict Biol 7:45–53

    Article  PubMed  Google Scholar 

  • Patkar AA, Mannelli P, Certa KM, Peindl K, Murray H, Vergare MJ, Berrettini WH (2004) Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence. Psychopharmacology (Berl) 76:74–81

    Article  Google Scholar 

  • Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E, Chen Y, Ma G, Klein DF (2002) Am J Psychiatry 159(11):1848–1854

    Article  PubMed  Google Scholar 

  • Rivier C (1993) Female rats release more corticosterone than males in response to alcohol: influence of circulating sex steroids and possible consequences for blood alcohol levels. Alcohol Clin Exp Res 17:854–859

    PubMed  Google Scholar 

  • Robbins SJ, Ehrman RN, Childress AR, O’Brien CP (1999) Comparing levels of cocaine cue reactivity in male and female outpatients. Drug Alcohol Depend 53:223–230

    Article  PubMed  Google Scholar 

  • Roelfsema F, van den Berg G, Frolich M, Veldhuis JD, van Eijk A, Buurman MM, Etman BH (1993) Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin. J Clin Endocrinol Metab 77:234–240

    Article  PubMed  Google Scholar 

  • Scott LV, Dinan TG (1998) Vasopressin and the regulation of hypothalamic–pituitary–adrenal axis function: implications for the pathophysiology of depression. Life Sci 62(22):1985–1998

    Article  PubMed  Google Scholar 

  • Seeman TE, Singer B, Wilkinson CW, McEwen B (2001) Gender differences in age-related changes in HPA axis reactivity. Psychoneuroendocrinology 26:225–240

    Article  PubMed  Google Scholar 

  • Silva C, Ines LS, Nour D, Straub RH, da Silva JA (2002) Differential male and female adrenal cortical steroid hormone and cortisol responses to interleukin-6 in humans. Ann N Y Acad Sci 966:68–72

    PubMed  Google Scholar 

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

    Article  Google Scholar 

  • Sinha R, Rounsaville BJ (2002) Sex differences in depressed substance abusers. J Clin Psychiatry 63:616–627

    PubMed  Google Scholar 

  • Sinha R, Catapano D, O’Malley S (1999) Stress-induced craving and stress response in cocaine dependent individuals. Psychopharmacology (Berl) 142:251–343

    Google Scholar 

  • Sinha R, Fuse T, Aubin LR, O’Malley SS (2000) Psychological stress, drug-related cues and cocaine craving. Psychopharmacology (Berl) 152:140–148

    Article  Google Scholar 

  • Sinha R, Talih M, Malison R, Cooney N, Anderson GM, Kreek MJ (2003) Hypothalamic–pituitary–adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl) 170:62–72

    Article  Google Scholar 

  • Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ Stress-induced cocaine craving and HPA responses predict cocaine relapse outcomes. Arch Gen Psychiatry (in press)

  • Sonne SC, Back SE, Diaz Zuniga C, Randall CL, Brady KT (2003) Gender differences in individuals with comorbid alcohol dependence and post-traumatic stress disorder. Am J Addict 12:412–423

    Google Scholar 

  • Sterling RC, Dean J, Weinstein SP, Murphy J, Gottheil E (2004) Gender differences in cue exposure reactivity and 9-month outcome. J Subst Abuse Treat 27:39–44

    Article  PubMed  Google Scholar 

  • Stoney CM, Matthews KA, McDonald RH, Johnson CA (1988) Sex differences in lipid, lipoprotein, cardiovascular, and neuroendocrine responses to acute stress. Psychophysiology 25:645–656

    PubMed  Google Scholar 

  • Stroud LR, Salovey P, Epel ES (2002) Sex differences in stress responses: social rejection versus achievement stress. Biol Psychiatry 52(4):318–327

    Article  PubMed  Google Scholar 

  • Taylor SE, Klein LC, Lewis BP, Gruenewald TL, Gurung RA, Updegraff JA (2000) Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight. Psychol Rev 107:411–429

    Article  PubMed  Google Scholar 

  • Teoh SK, Mendelson JH, Mello NK, Weiss R, McElroy S, McAfee B (1990) Hyperprolactinemia and risk for relapse of cocaine abuse. Biol Psychiatry 28:824–828

    Article  PubMed  Google Scholar 

  • Teoh SK, Lex BW, Mendelson JH, Mello NK, Cochin J (1992) Hyperprolactinemia and macrocytosis in women with alcohol and polysubstance dependence. J Stud Alcohol 53:176–182

    PubMed  Google Scholar 

  • Traustadóttir T, Bosch PR, Matt KS (2003) Gender differences in cardiovascular and hypothalamic–pituitary–adrenal axis responses to psychological stress in healthy older adult men and women. Stress 6:133–140

    PubMed  Google Scholar 

  • Tucker KA, Browndyke JN, Gottschalk PC, Cofrancesco AT, Kosten TR (2004) Gender-specific vulnerability for rCBF abnormalities among cocaine abusers. Neuroreport 15:797–801

    Article  PubMed  Google Scholar 

  • Weiss F (2005) Neurobiology of craving, conditioned reward and relapse. Curr Opin Pharmacol 5:9–19

    Article  PubMed  Google Scholar 

  • Yoshimura S, Sakamoto S, Kudo H, Sassa S, Kumai A, Okamoto R (2003) Sex-differences in adrenocortical responsiveness during development in rats. Steroids 68:439–445

    Article  PubMed  Google Scholar 

  • Zimmer C, Basler HD, Vedder H, Lautenbacher S (2003) Sex differences in cortisol response to noxious stress. Clin J Pain 19:233–239

    Article  PubMed  Google Scholar 

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Acknowledgements

We wish to thank the staff at the Substance Abuse Treatment Unit, Clinical Neuroscience Research Unit and the General Clinical Research Center at Yale University School of Medicine, and those at the Laboratory on the Biology of Addictive Diseases at Rockefeller University for their assistance in completing this study.

This study was supported in part by grants K02-DA17232 (Sinha), P50-DA16556 (Sinha), M01-RR00125 (Yale GCRC), K05-00049 (MJK) and P60-05130 (MJK) from the National Institutes of Health and its Office of Research on Women’s Health (ORWH), Bethesda, MD, USA.

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Authors and Affiliations

  1. Substance Abuse Center, Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, CT, 06519, USA

    Helen C. Fox, Miguel Garcia Jr, Kathleen Kemp, Verica Milivojevic & Rajita Sinha

  2. The Laboratory on the Biology of Addictive Diseases, Rockefeller University, NY, USA

    Mary Jeanne Kreek

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  1. Helen C. Fox
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  2. Miguel Garcia Jr
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  3. Kathleen Kemp
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  4. Verica Milivojevic
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  5. Mary Jeanne Kreek
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  6. Rajita Sinha
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Correspondence to Helen C. Fox.

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Fox, H.C., Garcia, M., Kemp, K. et al. Gender differences in cardiovascular and corticoadrenal response to stress and drug cues in cocaine dependent individuals. Psychopharmacology 185, 348–357 (2006). https://doi.org/10.1007/s00213-005-0303-1

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  • DOI: https://doi.org/10.1007/s00213-005-0303-1

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