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Effects of Neurotensin on the Effects of Pain Stress in Rats with Neurotoxic Lesions to Serotoninergic Structures of the Substantia Nigra of the Brain

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The aim of the present work was to study the effects of neurotensin on the behavior of rats with neurotoxic lesions to the serotoninergic structures of the substantia nigra of the brain. Changes in the reproduction of conditioned passive avoidance reactions were analyzed, as were changes in the effects of pain stimulation on the activity of rats in the open field. Administration of 5,7-dihydroxytryptamine into the substantia nigra was found to impair the reproduction of passive avoidance reactions and to weaken the suppressive effects of pain stimulation. Administration of the serotonin 5-HT1A receptor antagonist p-MPPF into the substantia nigra had similar effects on the effects of pain stimulation. Administration of neurotensin into the caudate nucleus before application of pain stimulation prevented the toxin-induced impairment to defensive behavior and its effects on motor activity. Administration of neurotensin into the substantia nigra 24 h after pain stimulation had no marked effect on the passive avoidance reaction but increased motor activity during its reproduction. The effects of giving neurotoxin into the substantia nigra were linked with weakening of the action of pain stress on motor activity. Prevention of the development of this effect in rats after microinjection of neurotensin into the caudate nucleus may be due to recovery of neurotoxin-impaired reproduction of passive avoidance and can be explained by normalization of the balance of interactions between the serotoninergic (5-HT) and dopaminergic systems of the brain.

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References

  1. N. I. Dubrovina, E. V. Popova, and R. Yu. Il’yuchenok, “Compensatory-restorative effects of quinpirole on extinction of a conditioned skill and amnesia in mice with alternative behavioral stereotypes,” Eksperim. Klin. Farmakol., 64, No. 3, 13–16 (2001).

    CAS  Google Scholar 

  2. N. I. Dubrovina and R. A. Tomilenko, “Characteristics of the extinction of a conditioned passive avoidance reflex in mice with different levels of anxiety,” Ros. Fiziol. Zh., 91, No. 9, 1013–1020 (2005).

    CAS  Google Scholar 

  3. E. V. Miroshnichenko, A. V. Stavrovskaya, N. P. Shugalin, et al., “Changes in the emotional state of rats on reproduction of passive avoidance reactions after administration of neurotensin into the nucleus accumbens of the brain,” Zh. Vyssh. Nerv. Deyat., 60, No. 6, 738–745 (2010).

    Google Scholar 

  4. G. F. Molodtsova, “Metabolism and receptor binding of serotonin in brain structures on reproduction of a conditioned passive avoidance reaction,” Zh. Vyssh. Nerv. Deyat., 54, No. 4, 433–441 (2004).

    Google Scholar 

  5. G. F. Molodtsova, “Different roles of dopamine and serotonin in the process of reproduction of a conditioned passive avoidance reaction in rats,” Zh. Vyssh. Nerv. Deyat., 56, No. 2, 242–246 (2006).

    CAS  Google Scholar 

  6. N. P. Shugalev, A. S. Ol’shanskii, G. Hartmann, and L. Lenard, “Effects of neurotensin on execution of active and passive avoidance motor reactions in rats with lesioned serotoninergic neurons,” Zh. Vyssh. Nerv. Deyat., 55, No. 2, 247–252 (2005).

    CAS  Google Scholar 

  7. N. P. Shugalev, A. V. Stavrovskaya, A. S. Ol’shanskii, et al., “Serotoninergic mechanisms of the effects of neurotensin on passive avoidance behavior in rats,” Zh. Vyssh. Nerv. Deyat., 57, No. 3, 341–346 (2007).

    Google Scholar 

  8. C. S. Alves, R. Andreatini, C. Cunha, et al., “Phosphatidylserine reverses reserpine-induced amnesia,” Eur. J. Pharmacol., 404, 161–167 (2000).

    Article  PubMed  CAS  Google Scholar 

  9. T. Antonelli, M. C. Tomasini, K. Fuxe, et al., “Receptor-receptor interactions as studied with microdialysis. Focus on NTR/D2 interactions in the basal ganglia,” J. Neural Transm., 114, No. 1, 105–113 (2007).

    Article  PubMed  CAS  Google Scholar 

  10. N. Azmi, C. Norman, C. H. Spicer, and G. W. Bennett, “Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task,” Behav. Pharmacol., 17, No. 4, 357–362 (2006).

    Article  PubMed  CAS  Google Scholar 

  11. S. Cabibl and S. Pugi-Allegra, “Opposite responses of mesolimbic dopamine system to controllable and uncontrollable aversive experiences,” J. Neurosci., 4, No. 5, 3333–3340 (1994).

    Google Scholar 

  12. K. C. Corley, T. H. Phan, W. P. Daugherty, et al., “Stress-induced activation of median raphe serotoninergic neurons in rats is potentiated by the neurotensin antagonist, SR 48692,” Neurosci. Lett., 319, 1–4 (2002).

    Article  PubMed  CAS  Google Scholar 

  13. B. R. Dilts, M. R. Novitzki, T. H. Phan, et al., “Neurotensin inhibits the activation of midbrain – serotoninergic neurons produced by random inescapable sound,” Brain Res., 742, No. 1–2, 294–298 (1996).

    Article  PubMed  CAS  Google Scholar 

  14. P. R. Dobner, “Neurotensin and pain modulation,” Peptides, 27, No. 10, 2405–2414 (2006).

    Article  PubMed  CAS  Google Scholar 

  15. C. S. Fawaz, P. Martel, D. Leo, and L. E. Trudeau, “Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function,” BMC Neurosci., 10, 96 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  16. L. Ferraro, M. C. Tomasini, K. Fuxe, et al., “Mesolimbic dopamine and cortico-accumbens glutamate afferents as major targets for the regulation of the ventral striato-pallidal GABA pathways by neurotensin peptides,” Brain Res. Rev., 55, No. 1, 144–154 (2007).

    Article  PubMed  CAS  Google Scholar 

  17. P. S. Goldman-Rakic, “The cortical dopamine system: role in memory and cognition,” Adv. Pharmacol., 42, 707–711 (1998).

    Article  PubMed  CAS  Google Scholar 

  18. F. G. Graeff, “On serotonin and experimental anxiety,” Psychopharmacology, 163, 467–476 (2002).

    Article  PubMed  CAS  Google Scholar 

  19. R. Grahn, M. Will, S. Hammack, et al., “Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor,” Brain Res., 826, 35–43 (1999).

    Article  PubMed  CAS  Google Scholar 

  20. L. Jennes, W. E. Stumpf, and P. W. Kalivas, “Neurotensin: topographical distribution in rat brain by immunohistochemistry,” J. Comp. Neurol., 210, 211–224 (1982).

    Article  PubMed  CAS  Google Scholar 

  21. J. Tolas and G. K. Aghajanian, “Neurotensin and the serotoninergic system,” Prog. Neurobiol., 52, 455–468 (1997).

    Article  Google Scholar 

  22. K. László, K. Tóth, E. Kertes, et al., “The role of neurotensin in passive avoidance learning in the rat central nucleus of amygdala,” Behav. Brain Res., 226, No. 2, 597–600 (2012).

    Article  PubMed  Google Scholar 

  23. M. Legault, P. Congar, and F. J. Michel, “Presynaptic action of neurotensin on cultured ventral tegmental area dopaminergic neurones,” Neuroscience, 111, 177–187 (2002).

    Article  PubMed  CAS  Google Scholar 

  24. A. H. Li, T. H. Yeh, and P. P. Tan, “Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus: ionic and molecular mechanisms,” Neuropharmacology, 40, 1073–1083 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. S. Maier, B. Kalman, and R. Grahn, “Chlordiazepoxide microinjected into the region of the dorsal raphe nucleus eliminates the interference with escape responding by inescapable shock whether administered before inescapable shock or escape testing,” Behav. Neurosci., 108, 121–130 (1994).

    Article  PubMed  CAS  Google Scholar 

  26. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego, 2nd edition (1986).

    Google Scholar 

  27. P. Petkova-Kirova, A. Rakovskaya, G. Zaekova, et al., “Stimulation by neurotensin of dopamine and 5-hydroxytryptamine (5-HT) release from rat prefrontal cortex: Possible role of NTR1 receptors in neuropsychiatric disorders,” Neurochem. Int., 53, No. 68, 355–361 (2008).

    Article  PubMed  CAS  Google Scholar 

  28. P. P. Rompre, “Psychostimulant-like effect of central microinjection of neurotensin on brain stimulation reward,” Peptides, 16, 1417–1420 (1995).

    Article  PubMed  CAS  Google Scholar 

  29. R. R. Rozeske, A. K. Evans, M. G. Frank, et al., “Uncontrollable, but not controllable, stress desensitizes 5-HT1A receptors in the dorsal raphe nucleus,” J. Neurosci., 31, No. 40, 107–115 (2011).

    Article  Google Scholar 

  30. R. J. Thielen and A. Frazer, “Effects of novel 5-HT1A receptor antagonists on measures of postsynaptic 5-HT1A receptor activation in vivo,” Life Sci., 56, PL163–PL168 (1995).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to N. G. Yamshchikova.

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*Deceased.

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 63, No. 3, pp. 384–394, May–June, 2013.

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Shugalev*, N.P., Stavrovskaya, A.V., Yamshchikova, N.G. et al. Effects of Neurotensin on the Effects of Pain Stress in Rats with Neurotoxic Lesions to Serotoninergic Structures of the Substantia Nigra of the Brain. Neurosci Behav Physi 44, 863–870 (2014). https://doi.org/10.1007/s11055-014-9994-2

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