Please wait a minute...
Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Front. Biol.    2017, Vol. 12 Issue (4) : 298-310    https://doi.org/10.1007/s11515-017-1455-1
RESEARCH ARTICLE
The role of dopamine D2 receptors in the amygdala in metabolic and behavioral responses to stress in male Swiss-Webster mice
Maryam Hassantash1, Hedayat Sahraei2, Zahra Bahari3, Gholam Hossein Meftahi2(), Roshanak Vesali1
1. Faculty of Psychology & Education, University of Tehran, Tehran, Iran
2. Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
3. Department of Physiology and Biophysics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
 Download: PDF(1358 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

OBJECTIVE: The D2 dopamine receptor is found in different parts of the amygdala. However, its contribution to stress is unknown. Thus, in the present study, we examined the effects of excitation and inhibition of D2 dopamine receptors in the amygdala on the metabolic and hormonal changes in response to stress.

METHODS: Bilateral amygdala cannulation was carried out in Swiss-Webster mice (n = 7). On recovery, different doses of the dopamine D2 receptor antagonist, sulpiride (1, 5 and 10 µg/mouse) or the dopamine D2 receptor agonist, bromocriptine (1, 5 and 10 µg/mouse) were injected into the amygdala. The animals were then placed in stress apparatus (communication box) where they received an electric shock (10 mV voltage, 10 Hz frequency and 60 s duration) after 30 min. The animal's activities were recorded for 10 min before and 10 min after the stress induction. Locomotion, rearing and freezing were investigated. Metabolic changes, such as food and water intake and anorexia, were studied.

RESULTS: The results show that stress increased the concentration of plasma corticosterone, which was followed by a decrease in locomotion and rearing and an increase in freezing behavior. Furthermore, both weight and water and food intake were reduced. Administration of bromocriptine led to a reduction of corticosterone at doses of 1 and 5 µg/mouse and an increase of corticosterone at 10 µg/mouse. Additionally, lower doses of bromocriptine (1 and 5 µg/mouse) caused an increase in locomotion and rearing and a decrease in freezing behavior. Similar results were observed with sulpiride injection.

CONCLUSION: D2 dopamine receptors can play a major role in the amygdala in stress. Both an agonist and an antagonist of the D2 receptor attenuate the metabolic and hormonal changes observed in response to stress

Keywords amygdala      anorexia      bromocriptine      corticosterone      D2 dopamine recepetor      sulpiride     
Corresponding Author(s): Gholam Hossein Meftahi   
Online First Date: 22 August 2017    Issue Date: 13 September 2017
 Cite this article:   
Maryam Hassantash,Hedayat Sahraei,Zahra Bahari, et al. The role of dopamine D2 receptors in the amygdala in metabolic and behavioral responses to stress in male Swiss-Webster mice[J]. Front. Biol., 2017, 12(4): 298-310.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-017-1455-1
https://academic.hep.com.cn/fib/EN/Y2017/V12/I4/298
Fig.1  The effect of bilateral intra-amygdala administration of different doses of bromocriptine (1, 5 or 10 µg/mouse) and induced stress on weight changes (A), food intake (B), water intake (C) and anorexia (D). The mice were investigated at a specific time every day for 14 consecutive days. The results obtained on the first day were taken as 100 and were used as a point of reference for measurements made on subsequent days (percentage).
Fig.2  Stress and bilateral intra-amygdala administration of bromocriptine induced changes in serum corticosterone concentrations. Five minutes before the stress, different doses of bromocriptine (1, 5 or 10 µg/mouse) or saline were injected bilaterally into the amygdala. Five minutes before the stress, saline bilateral was injected into the amygdala. To measure the serum corticosterone concentration, blood samples were taken from all mice on the first, seventh and fourteenth days after stress. The sample was taken from the corner of the animal’s eye after the experiment. The Mean±SEM are presented for 6 mice. ***P<0.001 shows a significant difference as compared to the negative control group (n = 7 mouse/group).
Fig.3  The effect of induced stress and bilateral intra-amygdala administration of different doses of bromocriptine (1, 5 or 10 µg/mouse) on dopamine related behavior. Changes in locomotion (A), rearing (B) and freezing time (C). ***P<0.001 shows a significant difference as compared to the negative control group.
Fig.4  The effect of the bilateral intra-amygdala administration of different doses of sulpiride (1, 5 or 10 µg/mouse) and induced stress on weight changes (A), food intake (B), water intake (C) and anorexia (D). The results obtained on the first day were taken as 100 and were used as a point of reference for measurements made on subsequent days (percentage).
Fig.5  Stress and bilateral intra-amygdala administration of different doses of sulpiride (1, 5 or 10 µg/mouse) induced changes in serum corticosterone concentrations. Five minutes before the stress, different doses of sulpiride (1, 5 or 10 µg/mouse) or saline were injected bilaterally into the amygdala. Five minutes before the stress, saline bilateral was injected into the amygdala. To measure the serum corticosterone concentration, blood samples were taken from all mice on the first, seventh and fourteenth days after stress. The samples were taken from the corner of the animals eyes after the experiment. The Mean±SEM are presented for 6 mice. ** P<0.01 and ***P<0.001 show a significant difference as compared to the negative control group. (n = 7 mouse/group)
Fig.6  Effects of bilateral intra-amygdala administration of different doses of sulpiride (1, 5 or 10 µg/mouse) on dopamine related behavior before stress. Changes in locomotion (A), rearing (B), and freezing time (C). ***P<0.001 shows a significant difference as compared to the negative control group. + + P<0.01 and+ P<0.05 shows a significant difference as compared to the positive control group. (n = 7 mouse/group).
1 Alcaro A, Huber R, Panksepp J (2007). Behavioral functions of the mesolimbic dopaminergic system: an affective neuroethological perspective. Brain Res Brain Res Rev, 56(2): 283–321
https://doi.org/10.1016/j.brainresrev.2007.07.014 pmid: 17905440
2 Anzalone A, Lizardi-Ortiz J E, Ramos M, De Mei C, Hopf F W, Iaccarino C, Halbout B, Jacobsen J, Kinoshita C, Welter M, Caron M G, Bonci A, Sulzer D, Borrelli E (2012). Dual control of dopamine synthesis and release by presynaptic and postsynaptic dopamine D2 receptors. J Neurosci, 32(26): 9023–9034
https://doi.org/10.1523/JNEUROSCI.0918-12.2012 pmid: 22745501
3 Asalgoo G, Jahromi G P, Meftahi G H, Sahraei H (2015). Posttraumatic Stress Disorder (PTSD): Mechanisms and Possible Treatments. Neurophysiology, 47(6): 482–489
https://doi.org/10.1007/s11062-016-9559-9
4 Bahari Z, Manaheji H, Dargahi L, Daniali S, Norozian M, Meftahi G H, Sadeghi M (2015). Time Profile of nNOS Expression in the Spinal Dorsal Horn after L5 Spinal Root Transection in Rats. Neurophysiology, 47(4): 287–294
https://doi.org/10.1007/s11062-015-9535-9
5 Bahari Z, Manaheji H, Hosseinmardi N, Meftahi G H, Sadeghi M, Danialy S, Noorbakhsh S M (2014). Induction of spinal long-term synaptic potentiation is sensitive to inhibition of neuronal NOS in L5 spinal nerve-transected rats. EXCLI J, 13: 751–760
pmid: 26417298
6 Belda X, Armario A (2009). Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis. Psychopharmacology (Berl), 206(3): 355–365
https://doi.org/10.1007/s00213-009-1613-5 pmid: 19621214
7 Belujon P, Grace AA (2015). Regulation of dopamine system responsivity and its adaptive and pathological response to stress. Proc R Soc Lond B Biol Sci, 282(1805): 20142516
8 Bissière S, Humeau Y, Lüthi A (2003). Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci, 6(6): 587–592
https://doi.org/10.1038/nn1058 pmid: 12740581
9 Brake W G, Zhang T Y, Diorio J, Meaney M J, Gratton A (2004). Influence of early postnatal rearing conditions on mesocorticolimbic dopamine and behavioural responses to psychostimulants and stressors in adult rats. Eur J Neurosci, 19(7): 1863–1874
https://doi.org/10.1111/j.1460-9568.2004.03286.x pmid: 15078560
10 Brandão M L, de Oliveira A R, Muthuraju S, Colombo A C, Saito V M, Talbot T (2015). Dual role of dopamine D(2)-like receptors in the mediation of conditioned and unconditioned fear. FEBS Lett, 589(22): 3433–3437
https://doi.org/10.1016/j.febslet.2015.02.036 pmid: 25783771
11 Bruijnzeel A W, Stam R, Compaan J C, Wiegant V M (2001). Stress-induced sensitization of CRH-ir but not P-CREB-ir responsivity in the rat central nervous system. Brain Res, 908(2): 187–196
https://doi.org/10.1016/S0006-8993(01)02646-4 pmid: 11454329
12 Cabib S, Puglisi-Allegra S (1996). Stress, depression and the mesolimbic dopamine system. Psychopharmacology (Berl), 128(4): 331–342
https://doi.org/10.1007/s002130050142 pmid: 8986003
13 Casolini P, Kabbaj M, Leprat F, Piazza P V, Rougé-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(1-2): 311–314
https://doi.org/10.1016/0006-8993(93)90836-C pmid: 8242373
14 Chalabi-Yani D, Sahraei H, Meftahi G H, Hosseini S B, Sadeghi-Gharajehdaghi S, Ali Beig H, Bourbour Z, Ranjabaran M (2015). Effect of transient inactivation of ventral tegmental area on the expression and acquisition of nicotine-induced conditioned place preference in rats. Iran Biomed J, 19(4): 214–219
pmid: 26210948
15 Chang C H, Grace A A (2013). Amygdala  b-noradrenergic receptors modulate delayed downregulation of dopamine activity following restraint. J Neurosci, 33(4): 1441–1450
https://doi.org/10.1523/JNEUROSCI.2420-12.2013 pmid: 23345220
16 Chrousos G P (2009). Stress and disorders of the stress system. Nat Rev Endocrinol, 5(7): 374–381
https://doi.org/10.1038/nrendo.2009.106 pmid: 19488073
17 Dalooei J R, Sahraei H, Meftahi G H, Khosravi M, Bahari Z, Hatef B, Mohammadi A, Nicaeili F, Eftekhari F, Ghamari F, Hadipour M, Kaka G (2016). Temporary amygdala inhibition reduces stress effects in female mice. J Adv Res, 7(5): 643–649
https://doi.org/10.1016/j.jare.2016.06.008 pmid: 27489731
18 De Mei C, Ramos M, Iitaka C, Borrelli E (2009). Getting specialized: presynaptic and postsynaptic dopamine D2 receptors. Curr Opin Pharmacol, 9(1): 53–58
https://doi.org/10.1016/j.coph.2008.12.002 pmid: 19138563
19 Diaz M R, Chappell A M, Christian D T, Anderson N J, McCool B A (2011). Dopamine D3-like receptors modulate anxiety-like behavior and regulate GABAergic transmission in the rat lateral/basolateral amygdala. Neuropsychopharmacology, 36(5): 1090–1103
https://doi.org/10.1038/npp.2010.246 pmid: 21270771
20 Dziedzicka-Wasylewska M, Willner P, Papp M (1997). Changes in dopamine receptor mRNA expression following chronic mild stress and chronic antidepressant treatment. Behav Pharmacol, 8(6-7): 607–618
https://doi.org/10.1097/00008877-199711000-00017 pmid: 9832973
21 Ehteram B Z, Sahraei H, Meftahi G H, Khosravi M (2017). Effect of Intermittent Feeding on Gonadal Function in Male And Female NMRI Mice During Chronic Stress. Braz Arch Biol Technol, 60: e17160607
22 Erfani M, Sahraei H, Bahari Z, Meftah G H, Hatef B, Mohammadi A, Hosseini S H (2017). Evaluation of the effect of time change in cognitive function in volunteers in Tehran. Glob J Health Sci, 9(2): 119–126
https://doi.org/10.5539/gjhs.v9n2p119
23 Ghobadi N, Sahraei H, Meftahi G H, Bananej M, Salehi S (2016). Effect of estradiol replacement in ovariectomized NMRI mice in response to acute and chronic stress. J Appl Pharm Sci, 6(11): 176–184
https://doi.org/10.7324/JAPS.2016.601128
24 Ghodrat M, Sahraei H, Razjouyan J, Meftahi G H (2014). Effects of a Saffron Alcoholic Extract on Visual Short-Term Memory in Humans: a Psychophysical Study Neurophysiol, 46(3): 247–253
25 Ginsberg A B, Campeau S, Day H E, Spencer R L (2003). Acute glucocorticoid pretreatment suppresses stress-induced hypothalamic-pituitary-adrenal axis hormone secretion and expression of corticotropin-releasing hormone hnRNA but does not affect c-fos mRNA or fos protein expression in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol, 15(11): 1075–1083
https://doi.org/10.1046/j.1365-2826.2003.01100.x pmid: 14622438
26 Girotti M, Pace T W W, Gaylord R I, Rubin B A, Herman J P, Spencer R L (2006). Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain. Neuroscience, 138(4): 1067–1081
https://doi.org/10.1016/j.neuroscience.2005.12.002 pmid: 16431027
27 Goldstein L E, Rasmusson A M, Bunney B S, Roth R H (1996). Role of the amygdala in the coordination of behavioral, neuroendocrine, and prefrontal cortical monoamine responses to psychological stress in the rat. J Neurosci, 16(15): 4787–4798
pmid: 8764665
28 Habib K E, Gold P W, Chrousos G P (2001). Neuroendocrinology of stress. Endocrinol Metab Clin North Am, 30(3): 695–728, vii–viii
https://doi.org/10.1016/S0889-8529(05)70208-5 pmid: 11571937
29 Herman J P, Mueller N K, Figueiredo H (2004). Role of GABA and glutamate circuitry in hypothalamo-pituitary-adrenocortical stress integration. Ann N Y Acad Sci, 1018(1): 35–45
https://doi.org/10.1196/annals.1296.004 pmid: 15240350
30 Hill M N, McLaughlin R J, Bingham B, Shrestha L, Lee T T, Gray J M, Hillard C J, Gorzalka B B, Viau V (2010). Endogenous cannabinoid signaling is essential for stress adaptation. Proc Natl Acad Sci USA, 107(20): 9406–9411
https://doi.org/10.1073/pnas.0914661107 pmid: 20439721
31 Hölzel B K, Carmody J, Evans K C, Hoge E A, Dusek J A, Morgan L, et al. (2009). Stress reduction correlates with structural changes in the amygdala. Soc Cogn Affect Neurosci, 23: nsp034
pmid: 19776221
32 Hosseini SB, Sahraei H, Mohammadi A, Hatef B, Meftahi GH, Chalabi-Yani D, et al.et al. (2015). Inactivation of the Nucl. accumbens core exerts no effect on nicotine-induced conditioned place preference. Neurophysiol 47: 295–301
33 Husseini Y, Sahraei H, Meftahi G H, Dargahian M, Mohammadi A, Hatef B, Zardooz H, Ranjbaran M, Hosseini S B, Alibeig H, Behzadnia M, Majd A, Bahari Z, Ghoshooni H, Jalili C, Golmanesh L (2016). Analgesic and anti-inflammatory activities of hydro-alcoholic extract of Lavandula officinalis in mice: possible involvement of the cyclooxygenase type 1 and 2 enzymes. Revista Brasileira de Farmacognosia, 26(1): 102–108
https://doi.org/10.1016/j.bjp.2015.10.003
34 Inglis F M, Moghaddam B (1999). Dopaminergic innervation of the amygdala is highly responsive to stress. J Neurochem, 72(3): 1088–1094
https://doi.org/10.1046/j.1471-4159.1999.0721088.x pmid: 10037480
35 Isovich E, Mijnster M J, Flügge G, Fuchs E (2000). Chronic psychosocial stress reduces the density of dopamine transporters. Eur J Neurosci, 12(3): 1071–1078
https://doi.org/10.1046/j.1460-9568.2000.00969.x pmid: 10762338
36 Jaferi A, Bhatnagar S (2006). Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress. Endocrinology, 147(10): 4917–4930
https://doi.org/10.1210/en.2005-1393 pmid: 16809449
37 Kasckow J W, Baker D, Geracioti T D Jr (2001). Corticotropin-releasing hormone in depression and post-traumatic stress disorder. Peptides, 22(5): 845–851
https://doi.org/10.1016/S0196-9781(01)00399-0 pmid: 11337099
38 Kim J G, Jung H S, Kim K J, Min S S, Yoon B J (2013). Basal blood corticosterone level is correlated with susceptibility to chronic restraint stress in mice. Neurosci Lett, 555: 137–142
https://doi.org/10.1016/j.neulet.2013.09.031 pmid: 24064064
39 Liu J, Garza J C, Li W, Lu X Y (2013). Melanocortin-4 receptor in the medial amygdala regulates emotional stress-induced anxiety-like behaviour, anorexia and corticosterone secretion. Int J Neuropsychopharmacol, 16(1): 105–120
https://doi.org/10.1017/S146114571100174X pmid: 22176700
40 McEwen B S (2007). Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev, 87(3): 873–904
https://doi.org/10.1152/physrev.00041.2006 pmid: 17615391
41 Meftahi G, Ghotbedin Z, Eslamizade M J, Hosseinmardi N, Janahmadi M (2015). Suppressive Effects of Resveratrol Treatment on The Intrinsic Evoked Excitability of CA1 Pyramidal Neurons. Cell J, 17(3): 532–539
pmid: 26464825
42 Meftahi G H, Janahmadi M, Eslamizade M J (2014). Effects of resveratrol on intrinsic neuronal properties of CA1 pyramidal neurons in rat hippocampal slices. Physiol Pharmacol, 18(2): 144–155
43 Missale C, Nash S R, Robinson S W, Jaber M, Caron M G (1998). Dopamine receptors: from structure to function. Physiol Rev, 78(1): 189–225
pmid: 9457173
44 Mohammadian Z, Sahraei H, Meftahi G H, Ali-Beik H (2017). Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat. Clin Exp Pharmacol Physiol, 44(3): 403–412
https://doi.org/10.1111/1440-1681.12715 pmid: 27997713
45 Motahari A A, Sahraei H, Meftahi G H (2016). Role of Nitric Oxide on Dopamine Release and Morphine-Dependency. Basic Clin Neurosci, 7(4): 283–290
pmid: 27872689
46 Paxinos G, Franklin K B J (2001) The mouse brain in stereotaxic coordinates. Second Ed.2 San Diego, Academic Press.
47 Perachon S, Schwartz J C, Sokoloff P (1999). Functional potencies of new antiparkinsonian drugs at recombinant human dopamine D1, D2 and D3 receptors. Eur J Pharmacol, 366(2-3): 293–300
https://doi.org/10.1016/S0014-2999(98)00896-6 pmid: 10082211
48 Pourhashemi S F, Sahraei H, Meftahi G H, Hatef B, Gholipour B (2016). The Effect of 20 Minutes Scuba Diving on Cognitive Function of Professional Scuba Divers. Asian J Sports Med, 7(3): e38633
https://doi.org/10.5812/asjsm.38633 pmid: 27826405
49 Puri S, Ray A, Chakravarti A K, Sen P (1994). Role of dopaminergic mechanisms in the regulation of stress responses in experimental animals. Pharmacol Biochem Behav, 48(1): 53–56
https://doi.org/10.1016/0091-3057(94)90497-9 pmid: 7913231
50 Rosen J B, Fanselow M S, Young S L, Sitcoske M, Maren S (1998). Immediate-early gene expression in the amygdala following footshock stress and contextual fear conditioning. Brain Res, 796(1-2): 132–142
https://doi.org/10.1016/S0006-8993(98)00294-7 pmid: 9689463
51 Rosenkranz J A, Grace A A (2002). Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning. Nature, 417(6886): 282–287
https://doi.org/10.1038/417282a pmid: 12015602
52 Sadeghi-Gharajehdaghi S, Sahraei H, Bahari Z, Meftahi GH, Jahromi GP, Ali-Beik H (2017). Effect of amygdaloid complex inhibition on nicotine-induced conditioned place preference in rats. J Appl Pharm Sci , 7(03):040–47
53 Sarabdjitsingh R A, Kofink D, Karst H, de Kloet E R, Joëls M (2012). Stress-induced enhancement of mouse amygdalar synaptic plasticity depends on glucocorticoid and ß-adrenergic activity. PLoS One, 7(8): e42143
https://doi.org/10.1371/journal.pone.0042143 pmid: 22900007
54 Schwartz G J, Zeltser L M (2013). Functional organization of neuronal and humoral signals regulating feeding behavior. Annu Rev Nutr, 33(1): 1–21
https://doi.org/10.1146/annurev-nutr-071812-161125 pmid: 23642202
55 Seeman P (2006). Targeting the dopamine D2 receptor in schizophrenia. Expert Opin Ther Targets, 10(4): 515–531
https://doi.org/10.1517/14728222.10.4.515 pmid: 16848689
56 Seo J H, Kuzhikandathil E V (2015). Dopamine D3 receptor mediates preadolescent stress-induced adult psychiatric disorders. PLoS One, 10(11): e0143908
https://doi.org/10.1371/journal.pone.0143908 pmid: 26619275
57 Trainor B C (2011). Stress responses and the mesolimbic dopamine system: social contexts and sex differences. Horm Behav, 60(5): 457–469
https://doi.org/10.1016/j.yhbeh.2011.08.013 pmid: 21907202
58 Vyas A, Bernal S, Chattarji S (2003). Effects of chronic stress on dendritic arborization in the central and extended amygdala. Brain Res, 965(1-2): 290–294
https://doi.org/10.1016/S0006-8993(02)04162-8 pmid: 12591150
59 Yamamoto R, Ueta Y, Kato N (2007). Dopamine induces a slow afterdepolarization in lateral amygdala neurons. J Neurophysiol, 98(2): 984–992
https://doi.org/10.1152/jn.00204.2007 pmid: 17553953
[1] Nima Heidary, Hedayat Sahraei, Mohammad Reza Afarinesh, Zahra Bahari, Gholam Hossein Meftahi. Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats[J]. Front. Biol., 2018, 13(2): 149-155.
[2] Sara Salehi Shemiran, Gholam Hossein Meftahi, Hedayat Sahraei, Negin Ghobadi. Effect of testosterone replacement on feeding behaviors after acute and chronic stress in gonadectomized male NMRI mice[J]. Front. Biol., 2017, 12(6): 430-441.
[3] M. A. Bottelier,A. Schrantee,G. van Wingen,H. G. Ruhé,M. B. de Ruiter,L. Reneman. A power analysis for future clinical trials on the potential adverse effects of SSRIs on amygdala reactivity[J]. Front. Biol., 2016, 11(3): 256-259.
[4] Qian ZHANG, Houkai LI, Feifan GUO. Amygdala, an important regulator for food intake[J]. Front Biol, 2011, 06(01): 82-85.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed