NEUROCHRMICAL MECHANISMS OF DISTURBANCES OF THE MENTAL PROCESSES UNDER LONG-TERM ADMINISTRATION OF GLUCOCORTICOIDS AND POSSIBLE ROUTES OF ITS CORRECTION
Abstract
Chronical administration with drinking-water of dexamethasone at dose 0,5 mg/kg/day–1 throughout 7 days rendered anxiogenic and prodepressive action and inhibited acquirement and retrieval of attainment of active avoidance conditioned reaction. It was revealed at experiments on horisontal slices of the medial prefrontal cortex decreasing of amplitudes of the field EPSPs of pyramidal neurons of cortical V layer and amplitudes of its NMDA components. It was revealed moreover an inhibition of long-term potentiation expression but facilitation of development of long-term depression. The psychopharmacological drugs used in our experiments only partially attenuated behavioral and neurochemical disturbances produced by dexamethasone. Only Ca2+ antagonist verapamil removed the manifestation of dexamethasone neurotoxicity at cellular and systemic levels at moderate degree. The obtained data allow to counsel
verapamil for attenuation of mental manifestation of side action of dexamethasone massive doses.
References
1. Абрамец И. И., Самойлович И. М., Талалаенко А. Н. Изменения свойств глутаматергических синапсов медиальной префронтальной коры и прилежащего ядра при поведенческой депрессии у крыс// Нейрофизиология.– 2007.– т. 39, No 3.– С. 214 – 221.
2. Дядык Ф. И., Багрий А. Э., Яровая Н. Ф.. Глюкокортикоидная терапия в клинической практике// Новости медицины и фармации.– 2009.– No 297.– С. 19 – 24.
3. Artola A. Diabetes-, stress-, and ageind-related changes in synaptic plasticty in hippocampus and neocortex – the same metaplastic process?// Eur. J. Pharmacol.– 2008.–vol. 585, No. 1.– P. 153 – 162.
4. Bidzinski A., Jankowska E., Pucilowski O. Antidrpressant-like action of nicardipine, verapamil and hemicholinium-3 injected into the anterior hypothalamus in the rat forced swim test//Pharmacol. Biochem. Behav.– 1990.– vol. 36, No 4.– P. 795 – 798.
5. Calton J. L., Kang M.–H., Wilson A. W., Moore S. D. NMDAreceptor-dependent synaptic activation of voltagedependent calcium channels in basolateral amygdala// J. Neurophysiol.– 2000.– vol. 83, No 2.– P. 685 – 692.
6. Cerqueira J. J., Pêgo J. M., Taipa R. et al. Morphological correlates of corticosteroid induced changes in prefrontal cortex-dependent behaviors// J Neurosci.– 2005.– vol. 25, No .– P. 7792 – 7800.
7. Cerqueira J. J., Mailliet F., Almeida O. F. et al. The prefrontal cortex as a key target of the maladaptive response to stress //J. Neurosci.– 2007.– vol. 27, No 10.– P. 2781–2787.
8. Clarke G., O`Mahony S. M., Cryan J. F., Dinan T. G. Verapamil in treatment resistant depression: a role for the P-glycoprotein transporter?// Neuropharmacol.– 2009.– vol. 24, No 3.– P. 217 – 223.
9. de Kloet E. R., M. Joëls M., F. Holsboer F. Stress and the brain: from adaptation to disease// Nat. Rev. Neurosci.– 2005.– vol. 6, No 4.– P. 463–475.
10. de Querian D. J., Roozendaal B., McGaugh J. L. Stress and glucocorticoids impair retrieval of long-term spatial memory// Nature.– 1998.– vol. 394, No 6695.– P. 787 – 790.
11. Donbolt N. C. Glutamate uptake// Progr. Neurobiol.– 2001.– vol. 65, No 1.– P. 1 – 105.
12. Goldman-Rakic P. M. Cellular basis of working memory// Neuron.– 1995.– vol. 14, No 2.– P. 477 – 485.
13. Gomes J. A., Stevens R. D., Levin J. J. et al. Glucocorticoid therapy in neurologic critical care// Crit. Care Med.– 2005.– vol. 33, No 6.– P. 1214 – 1224.
14. H aefely W . T he G ABA-benzodiazepine i nteraction: f ifteen years later// Neurochem. Res.– 1990.– vol. 15, No 2.– P. 169-174.
15. Hafezi-Moghadam A., Simoncini T., Yang Z. et al. Acute cardiovascular protective effect of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase// Nat. Med.– 2002.– vol. 8, No 5.– P. 473 – 479.
16. Handley S. L., Mithani S. Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration of “fear”- motivated behaviour// Naunyn-Smiedebergs Arch. Pharmacol.– 1984.– vol. 327, No. 1.– P. 1 – 5.
17. Hartley C. A., Phelps E. A. Changing fear: the neurocircuitry of emotion regulation// Neuropsychopharmacol.– 2010.– vol.35, No 1.– P. 136 – 146.
18. Herry C, Garcia R. Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice// J. Neurosci.– 2002.– vol. 22, No 2.– P. 577–583.
19. Hirsh J. C., Crepel F. Blockade of NMDA receptors unmasks a long-term depression in synaptic efficacy in rat prefrontal neurons in vitro// Exp. Brain Res.– 1991.– vol. 85, No 3.– P. 621 – 624.
20. Ilyin, V. I., Wittermore, E. R., Guastella, J. et al. (1996) Subtype selective inhibition of N–methyl-D-aspartate receptors by haloperidol// Mol. Pharmacol.– 1996.– vol. 50, No 6.– P. 1541 – 1550.
21. Izumi I., Auberson Y. P., Zorumski C. F. (2006) “Zinc modulates bidirectional hippocampal plasticity by effects on the NMDA receptors// J. Neurosci.– 2006.– vol. 26, No 27.– P. 7181 – 7188.
22. Kato A., N. Rouach N., R.A. Nicoll R. A., D.S. Bredt D. S. Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination// Proc. Natl. Acad. Sci. USA.– 2005.– vol. 102, No 6.– P. 5600–5605.
23. Keenan P. A., Jacobson M. W., Soleymani R. M. et al. The effect on memory of chronic prednisone treatment in patient with systemic disease// Neurology.– 1996.– vol. 47, No 6.– P. 1396 – 1402.
24. Knoll J., Kolemen K., Knoll B. A method for the elaborationof a non-extinguishable conditioned reflex in the rat”, Acta Physiol. Acad. Sci. Hung.– vol. 6, No. 2.– P. 327 – 345.
25. Leung D. Y., Hanifin J. M., Charlesworth E. N. et al. Disease management of atopic dermatitis: a practice parameter// Ann. Allergy Asthma Immunol.– 1997.– vol. 79, No 3.– P. 197 – 211.
26. Lin a., Hou Q., Jarzylo L. et al. Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking// J. Neurochem.– 2011.– vol. 119, No 1.– P. 27–39.
27. Liston M., Miller M., Goldwater D. S. et al. Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional setshifting// J. Neurosci.– 2006.– vol. 26, No 27.– P. 7870–7874.
28. Malenka R. C., Bear M. F. LTP and LTD: an embarrassment of riches// Neuron.– 2004.– vol. 44, No 1.– P. 5 – 21.
29. Matsumoto Y., Ohba Y., Ikeda N., Itoh M. Antidepressive action of Ca2+ channel antagonists on behavioral despair in forced swimming test in rats// Papers Kyushu Wom. Univer.– 2001.– vol. 37, No 4.– P. 27 – 34.
30. McEwen B. S. Physiology and neurobiology of stress and adaptation: central role of the brain// Physiol. Rev.– 2007.– vol. 87, No 4.– P. 873–904.
31. Mitra R., Jadhav S., McEwen B. S. et al. Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala// Proc. Natl. Acad. Sci. USA.– 2005.– vol. 102, No 10.– P. 9371–9376.
32. Mulder A. B., Nordquist R. E., Ôrgüt O., Pennartz C. M. A. Learning-related changes in response patterns of prefrontal neurons during instrumental conditioning// Behav. Brain Res.– 2003.– vol. 146, No 1.– P. 77–88.
33. Nakanishi S., Masu M. (1994) Molecular diversity and functions of glutamate receptors// Annu. Rev. Biophys. Biomol. Struct.– 1994.– vol. 23, No 3.– P. 319–348.
34. Peng L., Li B., Du T. et al. Does convential anti-bipolar and antidepressant drug therapy reduce NMDA-mediated neuronal excitation by downregulating astrocytic GluK2 function?// Pharmacol. Biochem. Behav.– 2012.– vol. 100, No 4.– P. 712-725.
35. Porsolt R. D. , A. Bertin A., and M. Jalfre M. “Behavioural despair” in rats and mice: strain differences and effects of imipramine// Eur. J. Pharmacol.– 1978.– vol. 51, No. 2.– P. 291 – 294.
36. Price J. L., Drevets W. C. Neurocircuitry of mood disorders// Neuropsychopharmacol.– 2010.– vol. 35, No 1.– P. 192 – 216.
37. Pucilowski, O., 1992. Psychopharmacological properties of calcium channel inhibitors// Psychopharmacology.– 1992.– vol. 109, No 1.– P. 12-29.
38. Radley J. J., Sisti H. M., Hao J. et al. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex // Neuroscience.– 2004.– vol. 125, No 1.– P. 1–6.
39. Radley J. J., Rocher A. B., Miller M. et al. Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex // Cereb. Cortex.– 2006.– vol. 16, No 3.– P. 313–320.
40. Rhen T., Cidlowski J. A. Antiinflammatory action of glucocorticoids – new mechanisms for old drugs// N. Engl. J. Med.–2005.– vol. 353, No 16.– P. 1711 – 1723.
41. Runyan J. D., Moore A. N., Dash P. K. A role for prefrontal cortex in memory storage for trace fear conditioning// J. Neurosci.– 2004.– vol. 24, No 5.– P. 1288–1295.
42. S ah P ., B ekkers J . M . A pical d endritic l ocationof s low afterhyperpolarization current in hippocampal pyramidal neurons: implication for the integration of long-term potentiation// J. Neurosci.– 1996.– vol. 16, No 15.– P. 4537- 4542.
43. Simons J. S., Sqiers H. J. Prefrontal and medial temporal lobe interactions in long-term memory// Nat. Rev. Neurosci.– 2003.– vol. 4, No 6.– P. 637–648.
44. Umukoro S., Ashorobi R. B., Essein E. E. 2006. Anticonvulsant and anxiolytic effects of calcium channel blockers in mice// J. Med. Sci.– 2006.– vol. 6, No 5.– P. 1021–1024.
45. Yuen E. Y., Liu W., Karatsoreos I. N. et al. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory// Proc. Natl. Acad. Sci. USA.– 2009.– vol. 106, No 15.– P. 14075–14079.
2. Дядык Ф. И., Багрий А. Э., Яровая Н. Ф.. Глюкокортикоидная терапия в клинической практике// Новости медицины и фармации.– 2009.– No 297.– С. 19 – 24.
3. Artola A. Diabetes-, stress-, and ageind-related changes in synaptic plasticty in hippocampus and neocortex – the same metaplastic process?// Eur. J. Pharmacol.– 2008.–vol. 585, No. 1.– P. 153 – 162.
4. Bidzinski A., Jankowska E., Pucilowski O. Antidrpressant-like action of nicardipine, verapamil and hemicholinium-3 injected into the anterior hypothalamus in the rat forced swim test//Pharmacol. Biochem. Behav.– 1990.– vol. 36, No 4.– P. 795 – 798.
5. Calton J. L., Kang M.–H., Wilson A. W., Moore S. D. NMDAreceptor-dependent synaptic activation of voltagedependent calcium channels in basolateral amygdala// J. Neurophysiol.– 2000.– vol. 83, No 2.– P. 685 – 692.
6. Cerqueira J. J., Pêgo J. M., Taipa R. et al. Morphological correlates of corticosteroid induced changes in prefrontal cortex-dependent behaviors// J Neurosci.– 2005.– vol. 25, No .– P. 7792 – 7800.
7. Cerqueira J. J., Mailliet F., Almeida O. F. et al. The prefrontal cortex as a key target of the maladaptive response to stress //J. Neurosci.– 2007.– vol. 27, No 10.– P. 2781–2787.
8. Clarke G., O`Mahony S. M., Cryan J. F., Dinan T. G. Verapamil in treatment resistant depression: a role for the P-glycoprotein transporter?// Neuropharmacol.– 2009.– vol. 24, No 3.– P. 217 – 223.
9. de Kloet E. R., M. Joëls M., F. Holsboer F. Stress and the brain: from adaptation to disease// Nat. Rev. Neurosci.– 2005.– vol. 6, No 4.– P. 463–475.
10. de Querian D. J., Roozendaal B., McGaugh J. L. Stress and glucocorticoids impair retrieval of long-term spatial memory// Nature.– 1998.– vol. 394, No 6695.– P. 787 – 790.
11. Donbolt N. C. Glutamate uptake// Progr. Neurobiol.– 2001.– vol. 65, No 1.– P. 1 – 105.
12. Goldman-Rakic P. M. Cellular basis of working memory// Neuron.– 1995.– vol. 14, No 2.– P. 477 – 485.
13. Gomes J. A., Stevens R. D., Levin J. J. et al. Glucocorticoid therapy in neurologic critical care// Crit. Care Med.– 2005.– vol. 33, No 6.– P. 1214 – 1224.
14. H aefely W . T he G ABA-benzodiazepine i nteraction: f ifteen years later// Neurochem. Res.– 1990.– vol. 15, No 2.– P. 169-174.
15. Hafezi-Moghadam A., Simoncini T., Yang Z. et al. Acute cardiovascular protective effect of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase// Nat. Med.– 2002.– vol. 8, No 5.– P. 473 – 479.
16. Handley S. L., Mithani S. Effects of alpha-adrenoceptor agonists and antagonists in a maze-exploration of “fear”- motivated behaviour// Naunyn-Smiedebergs Arch. Pharmacol.– 1984.– vol. 327, No. 1.– P. 1 – 5.
17. Hartley C. A., Phelps E. A. Changing fear: the neurocircuitry of emotion regulation// Neuropsychopharmacol.– 2010.– vol.35, No 1.– P. 136 – 146.
18. Herry C, Garcia R. Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice// J. Neurosci.– 2002.– vol. 22, No 2.– P. 577–583.
19. Hirsh J. C., Crepel F. Blockade of NMDA receptors unmasks a long-term depression in synaptic efficacy in rat prefrontal neurons in vitro// Exp. Brain Res.– 1991.– vol. 85, No 3.– P. 621 – 624.
20. Ilyin, V. I., Wittermore, E. R., Guastella, J. et al. (1996) Subtype selective inhibition of N–methyl-D-aspartate receptors by haloperidol// Mol. Pharmacol.– 1996.– vol. 50, No 6.– P. 1541 – 1550.
21. Izumi I., Auberson Y. P., Zorumski C. F. (2006) “Zinc modulates bidirectional hippocampal plasticity by effects on the NMDA receptors// J. Neurosci.– 2006.– vol. 26, No 27.– P. 7181 – 7188.
22. Kato A., N. Rouach N., R.A. Nicoll R. A., D.S. Bredt D. S. Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination// Proc. Natl. Acad. Sci. USA.– 2005.– vol. 102, No 6.– P. 5600–5605.
23. Keenan P. A., Jacobson M. W., Soleymani R. M. et al. The effect on memory of chronic prednisone treatment in patient with systemic disease// Neurology.– 1996.– vol. 47, No 6.– P. 1396 – 1402.
24. Knoll J., Kolemen K., Knoll B. A method for the elaborationof a non-extinguishable conditioned reflex in the rat”, Acta Physiol. Acad. Sci. Hung.– vol. 6, No. 2.– P. 327 – 345.
25. Leung D. Y., Hanifin J. M., Charlesworth E. N. et al. Disease management of atopic dermatitis: a practice parameter// Ann. Allergy Asthma Immunol.– 1997.– vol. 79, No 3.– P. 197 – 211.
26. Lin a., Hou Q., Jarzylo L. et al. Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking// J. Neurochem.– 2011.– vol. 119, No 1.– P. 27–39.
27. Liston M., Miller M., Goldwater D. S. et al. Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional setshifting// J. Neurosci.– 2006.– vol. 26, No 27.– P. 7870–7874.
28. Malenka R. C., Bear M. F. LTP and LTD: an embarrassment of riches// Neuron.– 2004.– vol. 44, No 1.– P. 5 – 21.
29. Matsumoto Y., Ohba Y., Ikeda N., Itoh M. Antidepressive action of Ca2+ channel antagonists on behavioral despair in forced swimming test in rats// Papers Kyushu Wom. Univer.– 2001.– vol. 37, No 4.– P. 27 – 34.
30. McEwen B. S. Physiology and neurobiology of stress and adaptation: central role of the brain// Physiol. Rev.– 2007.– vol. 87, No 4.– P. 873–904.
31. Mitra R., Jadhav S., McEwen B. S. et al. Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdala// Proc. Natl. Acad. Sci. USA.– 2005.– vol. 102, No 10.– P. 9371–9376.
32. Mulder A. B., Nordquist R. E., Ôrgüt O., Pennartz C. M. A. Learning-related changes in response patterns of prefrontal neurons during instrumental conditioning// Behav. Brain Res.– 2003.– vol. 146, No 1.– P. 77–88.
33. Nakanishi S., Masu M. (1994) Molecular diversity and functions of glutamate receptors// Annu. Rev. Biophys. Biomol. Struct.– 1994.– vol. 23, No 3.– P. 319–348.
34. Peng L., Li B., Du T. et al. Does convential anti-bipolar and antidepressant drug therapy reduce NMDA-mediated neuronal excitation by downregulating astrocytic GluK2 function?// Pharmacol. Biochem. Behav.– 2012.– vol. 100, No 4.– P. 712-725.
35. Porsolt R. D. , A. Bertin A., and M. Jalfre M. “Behavioural despair” in rats and mice: strain differences and effects of imipramine// Eur. J. Pharmacol.– 1978.– vol. 51, No. 2.– P. 291 – 294.
36. Price J. L., Drevets W. C. Neurocircuitry of mood disorders// Neuropsychopharmacol.– 2010.– vol. 35, No 1.– P. 192 – 216.
37. Pucilowski, O., 1992. Psychopharmacological properties of calcium channel inhibitors// Psychopharmacology.– 1992.– vol. 109, No 1.– P. 12-29.
38. Radley J. J., Sisti H. M., Hao J. et al. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex // Neuroscience.– 2004.– vol. 125, No 1.– P. 1–6.
39. Radley J. J., Rocher A. B., Miller M. et al. Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex // Cereb. Cortex.– 2006.– vol. 16, No 3.– P. 313–320.
40. Rhen T., Cidlowski J. A. Antiinflammatory action of glucocorticoids – new mechanisms for old drugs// N. Engl. J. Med.–2005.– vol. 353, No 16.– P. 1711 – 1723.
41. Runyan J. D., Moore A. N., Dash P. K. A role for prefrontal cortex in memory storage for trace fear conditioning// J. Neurosci.– 2004.– vol. 24, No 5.– P. 1288–1295.
42. S ah P ., B ekkers J . M . A pical d endritic l ocationof s low afterhyperpolarization current in hippocampal pyramidal neurons: implication for the integration of long-term potentiation// J. Neurosci.– 1996.– vol. 16, No 15.– P. 4537- 4542.
43. Simons J. S., Sqiers H. J. Prefrontal and medial temporal lobe interactions in long-term memory// Nat. Rev. Neurosci.– 2003.– vol. 4, No 6.– P. 637–648.
44. Umukoro S., Ashorobi R. B., Essein E. E. 2006. Anticonvulsant and anxiolytic effects of calcium channel blockers in mice// J. Med. Sci.– 2006.– vol. 6, No 5.– P. 1021–1024.
45. Yuen E. Y., Liu W., Karatsoreos I. N. et al. Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory// Proc. Natl. Acad. Sci. USA.– 2009.– vol. 106, No 15.– P. 14075–14079.
Published
2020-07-01
How to Cite
СИДОРОВА, Ю. В.; ЕВДОКИМОВ, Д. В.; АБРАМЕЦ, И. И..
NEUROCHRMICAL MECHANISMS OF DISTURBANCES OF THE MENTAL PROCESSES UNDER LONG-TERM ADMINISTRATION OF GLUCOCORTICOIDS AND POSSIBLE ROUTES OF ITS CORRECTION.
Архив клинической и экспериментальной медицины, [S.l.], v. 25, n. 1, p. 27-35, july 2020.
ISSN 1605-9360. Available at: <http://journal.dnmu.ru/index.php/akem/article/view/548>. Date accessed: 16 oct. 2025.
Section
Оригинальные исследования
