Abstract
The effects of the adrenocorticotropic hormone (ACTH(4–10)) analog, Semax (MEHFPGP), on the level of anxiety and depression in white rats have been studied in the normal state and against the back-ground of cholecystokinin-tetrapeptide (CCK-4) action. Semax was injected intranasally in doses of 50 and 500 μg/kg 15 min before the testing. CCK-4 was administered intraperitoneally in a dose of 400 μg/kg 40 min before the testing. The level of anxiety was estimated in the elevated plus-maze test, and the degree of depression, in the forced swimming test. Semax administration did not influence the emotional state of animals in the normal state. The CCK-4 injection led to an increase in anxiety and depression in rats. Semax normalized the animal behavior disturbed by the CCK-4 administration, which attests to its anxiolytic and antidepressant effects at elevated levels of anxiety and depression.
This is a preview of subscription content, access via your institution.
References
Megen van, H.J., Westenberg, H.G., Den Boer, J.A., and Kahn, R.S., The Panic-Inducing Properties of the Cholecystokinin Tetrapeptide CCK4 in Patients with Panic Disorder, Eur Neuropsychopharmacol., 1996, vol. 6, no. 3, pp. 187–194.
Megen van, H.J., Westenberg, H.G., Den Boer, J.A., et al., Effect of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on CCK-4 Induced Panic Attacks, Psychopharmacology (Berl)., 1997, vol. 129, no. 4, pp. 357–364.
Adan, A.H., Oosterom, J., Ludvigsdottir, G., et al., Identification of Antagonists for Melanocortin MC3, MC4 and MC5 Receptors, Eur. J. Pharmacol., 1994, vol. 269, pp. 331–337.
Ashmarin, I.P., Nezavibatko, V.N., Myasoedov, N.F., et al., Nootropic Analog of Adrenocorticotropic Hormone 4–10, Semax: Fifteen-Year Experience of Development, Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 1997, vol. 47, no. 2, pp. 420–430.
Ashmarin, I.P., Nezavibatko, V.N., Levitskaya, N.G., et al., Design and Investigation of an ACTH(4–10) Analogue Lacking D-Amino Acids and Hydrophobic Radicals, Neurosci. Res. Commun., 1995, vol. 16, no. 2, pp. 105–112.
Ashmarin, I.P., Rud’ko, O.I., Danilova, R.A., and Andreeva, L.A., Postponed Effect of Cholecystokinin Fragments 30–33 (CCK-4) and 31–33 (CCK-3), on Albino Rats Behavior, Neurosci. Res. Comm., 2004, vol. 34, no. 3, pp. 165–173.
Catania, A., Gatti, S., Colombo, G., and Lipton, J.M., Targeting Melanocortin Receptors As a Novel Strategy to Control Inflammation, Pharmacol. Rev., 2004, vol. 56, no. 1, pp. 1–29.
Chaki, S. and Okuyama, S., Involvement of Melanocortin-4 Receptor in Anxiety and Depression, Peptides, 2005, vol. 26, pp. 1952–1964.
Clarke, A. and File, S.E., Social and Exploratory Behavior in the Rat After Septal Administration of ORG 2766 and ACTH(4–10), Psychoneuroendocrinology, 1983, vol. 8, no. 3, pp. 343–350.
Cone, R.D., Anatomy and Regulation of the Central Melanocortin System, Nature Neurosci., 2005, vol. 8, pp. 571–578.
Detke, M.J., Rickels, M., and Lucki, I., Active Behaviors in the Rat Forced Swimming Test Differentially Produced by Serotonergic and Noradrenergic Antidepressants, Psychopharmacology (Berl.), 1995, vol. 121, no. 1, pp. 66–72.
Eremin, K.O., Kudrin, V.S., Saransaari, P., et al., Semax, an ACTH(4–10) Analogue with Nootropic Properties, Activates Dopaminergic and Serotoninergic Brain System in Rodent, Neurochem. Res., 2005, vol. 30, no. 12, pp. 1493–1500.
Getsova, V.M., Orlova, N.V., Folomkina, A.A., and Nezavibat’ko, V.N., Effect an ACTH Analog on the Processes of Learning and Memory in Rats, Zh. Vyssh. Nervn. Deyat. im. I.P. Pavlova, 1988, vol. 38, no. 6, pp. 1041–1047.
Goyal, S.N., Kokare, D.M., Chopde, C.D., and Subhedar, N.K., Alpha-Melanocyte Stimulating Hormone Antagonizes Antidepressant-Like Effect of Neuropeptide Y in Porsolt’s Test in Rats, Pharmacol. Biochem. Behav., 2006, vol. 85, no. 2, pp. 369–377.
Gusev, E.I., Skvortsova, V.I., Myasoedov, N.F., et al., Effectiveness of Semax in Acute Period of Hemispheric Ischemic Stroke (a Clinical and Electrophysiological Study), Zh. Nevropatol. Psikhiatr. im. S.S. Korsakova, 1997, vol. 97, no. 6, pp. 26–34.
Kent, J.M., Coplan, J.D., and Gorman, J.M., Clinical Utility of the Selective Serotonin Reuptake Inhibitors in the Spectrum of Anxiety, Biol. Psychiatry, 1998, vol. 44, no. 9, pp. 812–824.
Kokare, D.M., Dandekar, M.P., Chopde, C.D., and Subhedar, N.K., Interaction between Neuropeptide Y and Alpha-Melanocyte Stimulating Hormone in Amygdala Regulates Anxiety in Rats, Brain Res., 2005, vol. 1043, nos. 1–2, pp. 107–114.
Koszycki, D., Torres, S., Swain, J.E., and Bradwejn, J., Central Cholecystokinin Activity in Irritable Bowel Syndrome, Panic Disorder, and Healthy Controls, Psychosom. Med., 2005, vol. 67, no. 4, pp. 590–595.
Levitskaya, N.G., Sebentsova, E.A., Andreeva, L.A., et al., Neuroprotective Effects of Semax in MPTP-Induced Disturbances of Brain Dopamine System, in Ros. Fiziol. Zhurn. im. I.M. Sechenova, 2002, vol. 88,issue 11, pp. 1369–1377.
Maron, E., Toru, I., Vasar, V., and Shlik, J., The Effect of 5-Hydroxytryptophan on Cholecystokinin-4-Induced Panic Attacks in Healthy Volunteers, J. Psychopharmacol., 2004, vol. 18, no. 2, pp. 194–199.
Megen, van H.J., Westenberg, H.G., Den Boer, J.A., and Kahn, R.S. The panik-Inducing Properties of the Cholecystokinin Tetrapegtide CCK4 in Patients with Panic Disorder, Eur. Neuropsychopharmcol, 1996, vol. 9, no. 3, pp. 187–194.
Megen, van H.J., Westenberg, H.G., Den Boer, J.A., et al., Effectof the Selectie Serotonin Reuptake Inhibitor Fluvoxamine on CCK4 Induced Panic Attacks, Psychopharmacology (Berl.), 1997, vol. 129, no. 4, pp. 357–364.
Niesink, R.J. and van Ree, J.M., Analysis of the Facilitatory Effect of the ACTH(4–9) Analog ORG 2766 on Active Social Contact in Rats, Life Sci., 1984, vol. 34, no. 10, pp. 961–970.
Shimazaki, T. and Chaki, S., Anxiolytic-Like Effects of a Selective and Nonpeptidergic Melanocortin-4 Receptor Antagonist, MCL0129, in a Social Interaction Test, Pharmacol. Biochem. Behav., 2005, vol. 80, no. 3, pp. 195–400.
Starowicz, K. and Przewlocka, B., The Role of Melanocortins and Their Receptors in Inflammatory Processes, Nerve Regeneration and Nociception, Life Sci., 2003, vol. 73, no. 7, pp. 823–847.
Vilenskii, D.A., Levitskaya, N.G., Andreeva, L.A., et al., Effects of Chronic Semax Administration on Exploratory Activity and Emotional Reaction in White Rats, in Ros. Fiziol. Zhurn. im. I.M. Sechenova 2007, vol. 93,issue 6, pp. 661–669.
Wikberg, J.E.C., Muceniece, R., Mandrika, I., et al., New Aspects on the Melanocortins and Their Receptors, Pharmacol. Res., 2000, vol. 42, no. 5, pp. 393–420.
Wolterink, G. and van Ree, J.M., Stress-Induced Hypokinesia Is Facilitated by ACTH(7–10), Peptides, 1988, vol. 9, no. 2, pp. 277–282.
Wolterink, G. and van Ree, J.M., The ACTH4–9 Analog ORG 2766 “Normalizes” the Changes in Motor Activities of Rats Elicited by Housing and Test Conditions, Brain Res., 1987, vol. 421, nos. 1–2, pp. 41–47.
Yamano, Y., Yoshioka M., Toda Y. Et Al. Regulation of CRF, POMC and MC4R Gene Expression after Foot Shock Stress in the Rat Amygdale and Hypothalamus, J. Vet. Med. Sci., 2004, vol. 66, no. 11, pp. 1323–1327.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © N.G. Levitskaya, D.A. Vilenskii, E.A. Sebentsova, L.A. Andreeva, A.A. Kamensky, N.F. Myasoedov, 2010, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2010, No. 2, pp. 231–237.
Rights and permissions
About this article
Cite this article
Levitskaya, N.G., Vilenskii, D.A., Sebentsova, E.A. et al. Influence of semax on the emotional state of white rats in the norm and against the background of cholecystokinin-tetrapeptide action. Biol Bull Russ Acad Sci 37, 186–192 (2010). https://doi.org/10.1134/S1062359010020147
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1062359010020147
Keywords
- Emotional State
- Biology Bulletin
- Forced Swimming Test
- Active Swimming
- Elevated Plus Maze Test