Skip to main content

Advertisement

SpringerLink
Log in

Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis

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

Abstract

Rationale

Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not.

Objectives

We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats.

Results

Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO.

Conclusions

Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

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

Access this article

Log in via an institution

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

  • Armario A (2006) The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors? CNS Neurol Disord Drug Targets 5:485–501

    Article  PubMed  Google Scholar 

  • Assie MB, Dominguez H, Consul-Denjean N, Newman-Tancredi A (2006) In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles. Naunyn Schmiedebergs Arch Pharmacol 373:441–450

    Article  PubMed  CAS  Google Scholar 

  • Belda X, Marquez C, Armario A (2004) Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains. Behav Brain Res 154:399–408

    Article  PubMed  CAS  Google Scholar 

  • Berkenbosch F, Vermes I, Tilders FJ (1984) The beta-adrenoceptor-blocking drug propranolol prevents secretion of immunoreactive beta-endorphin and alpha-melanocyte-stimulating hormone in response to certain stress stimuli. Endocrinology 115:1051–1059

    Article  PubMed  CAS  Google Scholar 

  • Bitner RS, Nikkel AL, Otte S, Martino B, Barlow EH, Bhatia P, Stewart AO, Brioni JD, Decker MW, Moreland RB (2006) Dopamine D4 receptor signaling in the rat paraventricular hypothalamic nucleus: evidence of natural coupling involving immediate early gene induction and mitogen activated protein kinase phosphorylation. Neuropharmacology 50:521–531

    Article  PubMed  CAS  Google Scholar 

  • Borowsky B, Kuhn CM (1991) Monoamine mediation of cocaine-induced hypothalamo-pituitary-adrenal activation. J Pharmacol Exp Ther 256:204–210

    PubMed  CAS  Google Scholar 

  • Borowsky B, Kuhn CM (1992) D1 and D2 dopamine receptors stimulate hypothalamo-pituitary-adrenal activity in rats. Neuropharmacology 31:671–678

    Article  PubMed  CAS  Google Scholar 

  • Carrasco GA, Van de Kar LD (2003) Neuroendocrine pharmacology of stress. Eur J Pharmacol 463:235–272

    Article  PubMed  CAS  Google Scholar 

  • Casolini P, Kabbaj M, Leprat F, Piazza PV, Rouge-Pont F, Angelucci L, Simon H, Le Moal M, Maccari S (1993) Basal and stress-induced corticosterone secretion is decreased by lesion of mesencephalic dopaminergic neurons. Brain Res 622:311–314

    Article  PubMed  CAS  Google Scholar 

  • Charlton BG (1990) Adrenal cortical innervation and glucocorticoid secretion. J Endocrinol 126:5–8

    Article  PubMed  CAS  Google Scholar 

  • Cheung S, Ballew JR, Moore KE, Lookingland KJ (1998) Contribution of dopamine neurons in the medial zona incerta to the innervation of the central nucleus of the amygdala, horizontal diagonal band of Broca and hypothalamic paraventricular nucleus. Brain Res 808:174–181

    Article  PubMed  CAS  Google Scholar 

  • Czyrak A, Chocyk A, Mackowiak M, Fijal K, Wedzony K (2000) Distribution of dopamine D1 receptors in the nucleus paraventricularis of the hypothalamus in rats: an immunohistochemical study. Brain Res Mol Brain Res 85:209–217

    Article  PubMed  CAS  Google Scholar 

  • Dal-Zotto S, Marti O, Armario A (2002) Is repeated exposure to immobilization needed to induce adaptation of the hypothalamic-pituitary-adrenal axis? Influence of adrenal factors. Behav Brain Res 129:187–195

    Article  PubMed  CAS  Google Scholar 

  • Dal-Zotto S, Marti O, Delgado R, Armario A (2004) Potentiation of glucocorticoid release does not modify the long-term effects of a single exposure to immobilization stress. Psychopharmacology (Berl) 177:230–237

    Article  CAS  Google Scholar 

  • Dellu F, Piazza PV, Mayo W, Le Moal M, Simon H (1996) Novelty-seeking in rats—biobehavioral characteristics and possible relationship with the sensation-seeking trait in man. Neuropsychobiology 34:136–145

    Article  PubMed  CAS  Google Scholar 

  • Eaton MJ, Cheung S, Moore KE, Lookingland KJ (1996) Dopamine receptor-mediated regulation of corticotropin-releasing hormone neurons in the hypothalamic paraventricular nucleus. Brain Res 738:60–66

    Article  PubMed  CAS  Google Scholar 

  • Feldman S, Conforti N, Melamed E (1988) Hypothalamic norepinephrine mediates limbic effects on adrenocortical secretion. Brain Res Bull 21:587–590

    Article  PubMed  CAS  Google Scholar 

  • Feldman S, Weidenfeld J, Conforti N, Saphier D (1991) Differential recovery of adrenocortical responses to neural stimuli following administration of 5,7-dihydroxytryptamine into the hypothalamus. Exp Brain Res 85:144–148

    Article  PubMed  CAS  Google Scholar 

  • Finlay JM, Zigmond MJ (1997) The effects of stress on central dopaminergic neurons: possible clinical implications. Neurochem Res 22:1387–1394

    Article  PubMed  CAS  Google Scholar 

  • Foreman MM, Fuller RW, Hynes MD, Gidda JS, Nichols CL, Schaus JM, Kornfeld EC, Clemens JA (1989) Preclinical studies on quinelorane, a potent and highly selective D2-dopaminergic agonist. J Pharmacol Exp Ther 250:227–235

    PubMed  CAS  Google Scholar 

  • Fremeau RT Jr, Duncan GE, Fornaretto MG, Dearry A, Gingrich JA, Breese GR, Caron MG (1991) Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission. Proc Natl Acad Sci U S A 88:3772–3776

    Article  PubMed  CAS  Google Scholar 

  • Fuller RW, Snoddy HD (1981) Elevation of serum corticosterone concentrations in rats by pergolide and other dopamine agonists. Endocrinology 109:1026–1032

    Article  PubMed  CAS  Google Scholar 

  • Fuller RW, Snoddy HD (1984) Central dopamine receptors mediating pergolide-induced elevation of serum corticosterone in rats. Characterization by the use of antagonists. Neuropharmacology 23:1389–1394

    Article  PubMed  CAS  Google Scholar 

  • Garcia A, Armario A (2001) Individual differences in the recovery of the hypothalamic-pituitary-adrenal axis after termination of exposure to a severe stressor in outbred male Sprague-Dawley rats. Psychoneuroendocrinology 26:363–374

    Article  PubMed  CAS  Google Scholar 

  • Garcia A, Marti O, Valles A, Dal-Zotto S, Armario A (2000) Recovery of the hypothalamic-pituitary-adrenal response to stress. Effect of stress intensity, stress duration and previous stress exposure. Neuroendocrinology 72:114–125

    Article  PubMed  CAS  Google Scholar 

  • Giraud P, Lissitzky JC, Conte-Devolx B, Gillioz P, Oliver C (1980) Influence of haloperidol on ACTH and beta-endorphin secretion in the rat. Eur J Pharmacol 62:215–217

    Article  PubMed  CAS  Google Scholar 

  • Goebel S, Dietrich M, Jarry H, Wuttke W (1992) Indirect evidence to suggest that prolactin mediates the adrenal action of haloperidol to stimulate aldosterone and corticosterone secretion in rats. Endocrinology 130:914–919

    Article  PubMed  CAS  Google Scholar 

  • Hardin JW, Hilbe JM (2003) Generalized estimating equations. Chapman & Hall/CRC, Boca Raton, FL

    Google Scholar 

  • Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, Cullinan WE (2003) Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol 24:151–180

    Article  PubMed  CAS  Google Scholar 

  • Ikemoto S, Goeders NE (1998) Microinjections of dopamine agonists and cocaine elevate plasma corticosterone: dissociation effects among the ventral and dorsal striatum and medial prefrontal cortex. Brain Res 814:171–178

    Article  PubMed  CAS  Google Scholar 

  • Jezova D, Jurcovicova J, Vigas M, Murgas K, Labrie F (1985) Increase in plasma ACTH after dopaminergic stimulation in rats. Psychopharmacology (Berl) 85:201–203

    Article  CAS  Google Scholar 

  • Jorgensen H, Kjaer A, Warberg J, Knigge U (2001) Differential effect of serotonin 5-HT(1A) receptor antagonists on the secretion of corticotropin and prolactin. Neuroendocrinology 73:322–333

    Article  PubMed  CAS  Google Scholar 

  • Kan SF, Kau MM, Low-Tone Ho L, Wang PS (2003) Inhibitory effects of bromocriptine on corticosterone secretion in male rats. Eur J Pharmacol 468:141–149

    Article  PubMed  CAS  Google Scholar 

  • Kapetanovic IM, Sweeney DJ, Rapoport SI (1982) Age effects on haloperidol pharmacokinetics in male, Fischer-344 rats. J Pharmacol Exp Ther 221:434–438

    PubMed  CAS  Google Scholar 

  • Keim KL, Sigg EB (1977) Plasma corticosterone and brain catecholamines in stress: effect of psychotropic drugs. Pharmacol Biochem Behav 6:79–85

    Article  PubMed  CAS  Google Scholar 

  • Kile JP, Turner BB (1985) Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats. Experientia 41:1123–1127

    Article  PubMed  CAS  Google Scholar 

  • Kitchen I, Kelly M, Turner M (1988) Dopamine receptor modulation of corticosterone secretion in neonatal and adult rats. J Pharm Pharmacol 40:580–581

    PubMed  CAS  Google Scholar 

  • Knigge U, Warberg J (1991) The role of histamine in the neuroendocrine regulation of pituitary hormone secretion. Acta Endocrinol (Copenh) 124:609–619

    CAS  Google Scholar 

  • Knigge U, Matzen S, Bach FW, Bang P, Warberg J (1989) Involvement of histaminergic neurons in the stress-induced release of pro-opiomelanocortin-derived peptides in rats. Acta Endocrinol (Copenh) 120:533–539

    CAS  Google Scholar 

  • Lieben CK, Steinbusch HW, Blokland A (2006) 5,7-DHT lesion of the dorsal raphe nuclei impairs object recognition but not affective behavior and corticosterone response to stressor in the rat. Behav Brain Res 168:197–207

    Article  PubMed  Google Scholar 

  • Mansour A, Meador-Woodruff JH, Bunzow JR, Civelli O, Akil H, Watson SJ (1990) Localization of dopamine D2 receptor mRNA and D1 and D2 receptor binding in the rat brain and pituitary: an in situ hybridization-receptor autoradiographic analysis. J Neurosci 10:2587–2600

    PubMed  CAS  Google Scholar 

  • Marquez C, Belda X, Armario A (2002) Post-stress recovery of pituitary-adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations. Brain Res 926:181–185

    Article  PubMed  CAS  Google Scholar 

  • Marquez C, Nadal R, Armario A (2006) Influence of reactivity to novelty and anxiety on hypothalamic-pituitary-adrenal and prolactin responses to two different novel environments in adult male rats. Behav Brain Res 168:13–22

    Article  PubMed  CAS  Google Scholar 

  • Marti O, Garcia A, Valles A, Harbuz MS, Armario A (2001) Evidence that a single exposure to aversive stimuli triggers long-lasting effects in the hypothalamus-pituitary-adrenal axis that consolidate with time. Eur J NeuroSci 13:129–136

    Article  PubMed  CAS  Google Scholar 

  • Matsuki M, Nishida S, Kashiwa Y, Horino M, Yoneda M, Endoh M, Satoh A, Oyama H (1985) Effect of dopamine on ACTH-induced glucocorticoid secretion in rat adrenal suspended cells. Horm Metab Res 17:429–431

    Article  PubMed  CAS  Google Scholar 

  • Missale C, Memo M, Liberini P, Carruba MO, Spano P (1985) Evidence for the presence of D1 and D2 dopamine receptors in the rat adrenal cortex. Eur J Pharmacol 109:315–316

    Article  PubMed  CAS  Google Scholar 

  • Natesan S, Reckless GE, Nobrega JN, Fletcher PJ, Kapur S (2006) Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models. Neuropsychopharmacology 31:1854–1863

    Article  PubMed  CAS  Google Scholar 

  • Neisewander JL, Fuchs RA, O’Dell LE, Khroyan TV (1998) Effects of SCH-23390 on dopamine D1 receptor occupancy and locomotion produced by intraaccumbens cocaine infusion. Synapse 30:194–204

    Article  PubMed  CAS  Google Scholar 

  • Pivonello R, Ferone D, Lombardi G, Colao A, Lamberts SW, Hofland LJ (2007) Novel insights in dopamine receptor physiology. Eur J Endocrinol 156(Suppl 1):S13–S21

    Article  PubMed  CAS  Google Scholar 

  • Puri S, Ray A, Chakravarty AK, Sen P (1991) Role of histaminergic mechanisms in the regulation of some stress responses in rats. Pharmacol Biochem Behav 39:847–850

    Article  PubMed  CAS  Google Scholar 

  • Puri S, Ray A, Chakravarti AK, Sen P (1994) Role of dopaminergic mechanisms in the regulation of stress responses in experimental animals. Pharmacol Biochem Behav 48:53–56

    Article  PubMed  CAS  Google Scholar 

  • Richardson Morton KD, Van de Kar LD, Brownfield MS, Lorens SA, Napier TC, Urban JH (1990) Stress-induced renin and corticosterone secretion is mediated by catecholaminergic nerve terminals in the hypothalamic paraventricular nucleus. Neuroendocrinology 51:320–327

    Article  PubMed  CAS  Google Scholar 

  • Ritter S, Watts AG, Dinh TT, Sanchez-Watts G, Pedrow C (2003) Immunotoxin lesion of hypothalamically projecting norepinephrine and epinephrine neurons differentially affects circadian and stressor-stimulated corticosterone secretion. Endocrinology 144:1357–1367

    Article  PubMed  CAS  Google Scholar 

  • Rivier C, Vale W (1987) Diminished responsiveness of the hypothalamic-pituitary-adrenal axis of the rat during exposure to prolonged stress: a pituitary-mediated mechanism. Endocrinology 121:1320–1328

    Article  PubMed  CAS  Google Scholar 

  • Saller CF, Kreamer LD, Adamovage LA, Salama AI (1989) Dopamine receptor occupancy in vivo: measurement using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Life Sci 45:917–929

    Article  PubMed  CAS  Google Scholar 

  • Saphier D, Farrar GE, Welch JE (1995) Differential inhibition of stress-induced adrenocortical responses by 5-HT1A agonists and by 5-HT2 and 5-HT3 antagonists. Psychoneuroendocrinology 20:239–257

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Ulpian C (1988) Dopamine D1 and D2 receptor selectivities of agonists and antagonists. Adv Exp Med Biol 235:55–63

    PubMed  CAS  Google Scholar 

  • Seltzer AM, Donoso AO, Podesta E (1986) Restraint stress stimulation of prolactin and ACTH secretion: role of brain histamine. Physiol Behav 36:251–255

    Article  PubMed  CAS  Google Scholar 

  • Spangler R, Zhou Y, Schlussman SD, Ho A, Kreek MJ (1997) Behavioral stereotypies induced by “binge” cocaine administration are independent of drug-induced increases in corticosterone levels. Behav Brain Res 86:201–204

    Article  PubMed  CAS  Google Scholar 

  • Spencer SJ, Ebner K, Day TA (2004) Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic-pituitary-adrenal axis responses to different stressors. Eur J NeuroSci 20:1008–1016

    Article  PubMed  CAS  Google Scholar 

  • Sullivan RM, Dufresne MM (2006) Mesocortical dopamine and HPA axis regulation: role of laterality and early environment. Brain Res 1076:49–59

    Article  PubMed  CAS  Google Scholar 

  • Swanson LW, Sawchenko PE (1980) Paraventricular nucleus: a site for the integration of neuroendocrine and autonomic mechanisms. Neuroendocrinology 31:410–417

    Article  PubMed  CAS  Google Scholar 

  • Taymans JM, Kia HK, Claes R, Cruz C, Leysen J, Langlois X (2004) Dopamine receptor-mediated regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections and time. Eur J NeuroSci 19:2249–2260

    Article  PubMed  Google Scholar 

  • Wagner CK, Eaton MJ, Moore KE, Lookingland KJ (1995) Efferent projections from the region of the medial zona incerta containing A13 dopaminergic neurons: a PHA-L anterograde tract-tracing study in the rat. Brain Res 677:229–237

    Article  PubMed  CAS  Google Scholar 

  • Wurzburger RJ, Miller RL, Marcum EA, Colburn WA, Spector S (1981) A new radioimmunoassay for haloperidol: direct measurement of serum and striatal concentrations. J Pharmacol Exp Ther 217:757–763

    PubMed  CAS  Google Scholar 

  • Zhou Y, Spangler R, Ho A, Jeanne Kreek M (2001) Hypothalamic CRH mRNA levels are differentially modulated by repeated ‘binge’ cocaine with or without D(1) dopamine receptor blockade. Brain Res Mol Brain Res 94:112–118

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Spangler R, Yuferov VP, Schlussmann SD, Ho A, Kreek MJ (2004) Effects of selective D1- or D2-like dopamine receptor antagonists with acute “binge” pattern cocaine on corticotropin-releasing hormone and proopiomelanocortin mRNA levels in the hypothalamus. Brain Res Mol Brain Res 130:61–67

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported by grants SAF2008-01175 (MEC) and RD06/0001/0015 (Instituto de Salud Carlos III, Redes temáticas de Investigación Cooperativa en Salud). Thanks are given to Roser Nadal for her help with the statistical analysis.

Author information

Authors and Affiliations

  1. Institut de Neurociències and Unitat de Fisiologia Animal (Facultat de Biociències), Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain

    Xavier Belda & Antonio Armario

Authors
  1. Xavier Belda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Armario
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Armario.

Additional information

Animal care

This research has been conducted according to the “Principles of laboratory animal care” and was carried out in accordance the European Communities Council Directive (86/609/EEC).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belda, X., Armario, A. Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis. Psychopharmacology 206, 355–365 (2009). https://doi.org/10.1007/s00213-009-1613-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1613-5

Keywords

Search

Navigation