Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 3, May-June, p. 307–312

Publication type: original article

Language: English

Effect of Phencyclidine Derivatives on Anxiety-like Behavior Using an Elevated-plus Maze Test in Mice

Ocena wpływu pochodnych fencyklidyny na zachowania lękowe za pomocą uniesionego labiryntu krzyżowego u myszy

Ramin Hajikhani1,, Abbas Ahmadi2,, Nima Naderi3,, Kayvan Yaghoobi3,, Zahra Shirazizand3,, Nazereh M. Rezaee2,, Babak N. Niknafs4,

1 Department of Physiology, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran

2 Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran

3 Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Islamic Azad University, Karaj branch, Karaj, Iran

Abstract

Objectives. The study attempted to investigate the anti-anxiety activities of Phencyclidine (1-(1-phenylcyclohexyl) piperidine, PCP, I) and some of its derivatives (M, F, L, B, S, P) with the elevated-plus maze (EPM) Test.
Material and Methods. Phencyclidine and its derivatives (M, F, L, B, S, P) were administrated intraperitoneally (i.p.) at a dose of 10 mg/kg to male mice. Anxiety-like behaviors were assessed using the elevated-plus maze test.
Results. EPM results revealed an increase in open arms time spent after applying PCP and M, L, P, and B compounds at the administered dosage. Moreover, an increase in the number of open arm entries was observed with M, P, and B compounds. The P, B and S compounds increased the locomotion of animals, too, which might be considered as the side effect to the compounds.
Conclusion. Considering the elevated-plus maze results, it was concluded that M and L compounds could be considered as a potential anxiolytic with less side effects due to a probable high electron donation of the methoxy group, as well as the hydrophilic properties of hydroxyl groups on these compounds.

Streszczenie

Cel pracy. Zbadanie przeciwlękowego działania fencyklidyny (1-(1- fenylocykloheksylo)piperydyny – PCP, I) i niektórych jej pochodnych (M, F, L, B, S, P) za pomocą uniesionego labiryntu krzyżowego (EPM).
Materiał i metody. Fencyklidynę i jej pochodne (M, K, L, B, S, P) podawano dootrzewnowo (ip) w dawce 10 mg/kg samcom myszy. Zachowania lękowe oceniano za pomocą uniesionego labiryntu krzyżowego.
Wyniki. Badanie EPM wykazało dłuższy czas pobytu na ramieniu otwartym po zastosowaniu PCP i związków M, L, P i B w podanej dawce. Ponadto zaobserwowano większą liczbę wejść na ramiona otwarte po podaniu związków M, P, B. Związki P, B i S wywołały także zwiększoną ruchliwość zwierząt, co może być uważane za działanie uboczne podanych związków.
Wnioski. Mając na uwadze wyniki badania za pomocą uniesionego labiryntu krzyżowego, stwierdzono, że związki M i L mogą być traktowane jako potencjalnie przeciwlękowe i wykazujące mniej działań ubocznych ze względu na prawdopodobnie duże dodawanie elektronów grupy metoksylowej, jak również właściwości hydrofilowe grup hydroksylowych tych związków.

Key words

phencyclidine derivatives, anxiety-like behavior, elevated-plus maze test, mice

Słowa kluczowe

pochodne fencyklidyny, zachowanie lękowe, uniesiony labirynt krzyżowy, myszy

References (29)

  1. Diagnostic and Statistical Manual of Mental Disorders Washington D.C.: American Psychiatric Association, 4, 2000.
  2. Lakhan SH E, Vieira KF: Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J 2010, 9, 42, 1–14.
  3. Kemp JA, Foster AC, Wong EHF: Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci 1987, 10, 294–298.
  4. Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA: NMDA antagonist neurotoxicity: mechanism and prevention. Science 1991, 254(5037), 1515–1518.
  5. Ahmadi A, Khalili M, Hajikhani R, Naserbakht M: New morpholine analogues of phencyclidine: Chemical synthesis and pain perception in rats. Pharmacol Biochem Behav 2011, 98, 227–233.
  6. Mori A, Noda Y, Mamiya T, Miamoto Y, Nakajima A, Furukawa H, Nabeshima T: Phencyclidine-induced discriminative stimulus is mediated via Phencyclidine binding sites on the N-methyl-D-asparate receptor-ion channel complex, not via sigma receptors. Behav Brain Res 2001, 119, 33–40.
  7. Geller EB, Adler LH, Wojno C, Adler MW: The Anticonvulsant Effect of Phencyclidine in Rats. Psychopharmacology 1981, 74, 97–98.
  8. Balster RL, Chait LD: The behavioral pharmacology of Phencyclidine. Clin Toxicol 1976, 9, 513–528.
  9. Hajkhani R, Solati J, Ahmadi A, Salari AA: The Effect of Phencyclidine New Derivatives on Anxiety Behaviors in Rats. Iran J Basic Med Sci 2010, 13 (2), 16–23.
  10. Woolverton WL, Balster RL: Tolerance to the behavioral effects of phencyclidine: the importance of behavioral and pharmacological variables. Psychopharmacology 1979, 64, 19–24.
  11. Lal H, Emmett-Oglesby MW: Behavioral analogues of anxiety animal models. Neuropharmacology 1983, 22, 1423–1441.
  12. Griez EJL: Anxiety Disorders: An Introduction to Clinical Management and Research. John Wiley and Sons 2001.
  13. Ninan PT: The functional anatomy, neurochemistry, and pharmacology of anxiety. J Clin Psychiatry 1999, 60 Suppl 22, 12–17.
  14. Maddox VH, Godefroi EF, Parcell RF: The synthesis of phencyclidine and other 1-arylcyclohexylamines. J Med Chem 1965, 8, 230–235.
  15. Ahmadi A, Solati J, Hajikhani R, Onagh M, Javadi M: Synthesis and analgesic effects of 1-[1-(2-methylphenyl)( cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice. Arzneim-Forsch/Drug Res 2010, 60, 492–496.
  16. Ahmadi A, Khalili M, Hajikhani R, Naserbakht M: Synthesis and determination of acute and chronic pain activities of 1-[1-(4-methylphenyl)(cyclohexyl)] morpholine as a new phencyclidine derivative in rats. Arzneim-Forsch/ Drug Res 2011, 61, 1–11.
  17. Ahmadi A, Khalili M, Hajikhani R, Barghi L, Mihandoust F: Synthesis and Determination of Chronic and Acute Thermal and Chemical Pain. Iran J Pharm Res 2010, 9 (4), 379–385.
  18. Ahmadi A, Khalili M, Abbassi S, Javadi M, Mahmoudi A, Hajikhani R: Synthesis and determination of acute and chronic pain activities of 1-[1-(4-methylphenyl)(cyclohexyl)] morpholine as a new phencyclidine derivative in rats. Arzneim-Forsch/Drug Res 2009, 59 (4), 202–206.
  19. Ahmadi A, Khalili M, Mihandoust F, Barghi L: Synthesis and determination of acute and chronic pain activities of 1-[1-[3-methyphenyl] [tetralyl]] piperidine as a new derivative of phencyclidine via tail immersion and formalin tests. Arzneim-Forsch/Drug Res 2010, 60(1), 30–35.
  20. Lister RG: The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berlin) 1987, 92, 180–185.
  21. Kinnard WR, Carr CJ: A preliminary procedure for evaluation of central nervous system depressants. J Pharmacol Exp Ther 1957, 121, 354–356.
  22. Stephens DN, Meldrum BS, Weidmann R: Does the excitatory amino acid receptor antagonist 2-APH exhibit anxiolytic activity? Psychopharmacology (Berlin) 1986, 90, 166–169.
  23. Fryer JD, Lukas RJ: Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. J Pharmacol Exp Ther 1999, 288 (1), 88–92.
  24. Zarrindast MR, Solati J, Oryan S, Parivar K: Effect of intra-amygdala injection of nicotine and gaba receptor agents on anxiety-like behavior in rats. Pharmacology 2008, 82, 276–284.
  25. Adamec R: Transmitter systems involved in neural plasticity underlying increased anxiety and defense-Implications for understanding anxiety following traumatic stress. Neurosci Biobehav Rev 1997, 21, 755–765.
  26. Ochoa EL, Li L, McNamee MG: Desensitization of central cholinergic mechanisms and neuroadaptation to nicotine. Mol Neurobiol 1990, 4, 251–287.
  27. Olney J, Newcomer J: NMDA receptor hypofunction model of schizophrenia. J Psychiatry Res 1999, 33, 523– 533.
  28. Martin P, Carlsson M: Systemic PCP treatment elevates brain extracellular 5-H-T: a microdialysis study in awake rats. Neuroreport 1998, 9, 2985.
  29. Graeff F, Guimarães F: Role of 5-HT in stress, anxiety, and depression. Pharmacol Biochem Behav 1996, 54, 129–142.