The Effects of Intra-Amygdala Injection of Nicotine and Harmaline on Anxiey-Related Behavior in Adult Male Rat


Department of Biology, Faculty of Sciences, Damghan Branch, Islamic Azad University, Damghan, Iran


B-carboline alkaloids such as harmaline and nicotine are naturally present in the human food chain. Plants which contain B-caroline have anxiety and hallucinogenic effects. In this study the change in like – anxiety behaviors was investigated after intra- amygdala injections of nicotine and harmaline and intra action of them in male rat. Different doses of Harmaline, Nicotine and its compounds were applied for 30 minutes, before test of anxiety injection to (CeA) amygdale. Then like anxiety behavior include open arm time and Locomotor activity, spent open arm time, entriar open arm in maze were examined for 5 minute . Bilateral injection of Harmaline and Nicotine was decreased in to (CeA) amygdale one-by- one open arm times in control group. Injections of effective does of Nicotine could increase anxiety effects of Harmaline. Furthermore, Injection of ineffective doses of drugs has increased anxiety. The results show that Harmaline and Nicotine have anxiety effects. Also muscarinic and Nicotine receptor have important role in Like- anxiety behaviors. Acetylcholine in CeA amygdale thorough Nicotine receptors caused anxiety behaviors. Joined injection increased them effective.


  1. Akiyama K, Sutoo D. The relationship
  2. betweenstress and epilepsy. Eur J Pharmacol
  3. ; 183:227
  4. Arib O, Rat P, Molimard R, Chait A, Faure P, de
  5. Beaurepaire R. Electrophysiological
  6. characterization of harmane-induced activation
  7. of mesolimbic dopamine neurons. Eur J
  8. Pharmacol 2010; 629(1-3): 47-52-
  9. Bueno CH, Zangrossi H, Jr., Viana MB. The
  10. inactivation of the basolateral nucleus of the rat
  11. amygdala has an anxiolytic effect in the
  12. elevated T-mazeand light/dark transition tests.
  13. Braz J Med Biol Res 2005; 38: 1697-1701.
  14. Cortese BM, Phan KL. The role of glutamate
  15. inanxiety and related disorders. CNS Spectr
  16. ; 10(10):820-30.
  17. Davis M, Shi C. The extended amygdala: are
  18. thecentral nucleus of the amygdala and the
  19. bednucleus of the stria terminalis differentially
  20. involved in fear versus anxiety? Ann N Y Acad
  21. Sci 1999; 877: 281-91
  22. File SE, Kenny PJ, Cheeta S. The role of the
  23. dorsal hippocampal serotonergic and
  24. cholinergic systems in the modulation of
  25. anxiety. Pharmacology, biochemistry, and
  26. behavior 2000; 66: 65-72
  27. Freedland CS, Mansbach RS. Behavioral profile
  28. of constituents in ayahuasca, an Amazonian
  29. psychoactive plant mixture. Drug Alcohol
  30. Depend 1999; 54:183-94
  31. Fuentes JA,Longo VG.Aninvestigation on the
  32. central effects of harmine,harmaline and related
  33. beta-Carbolines.Neuropharmacology.1971.10(
  34. :15-23.
  35. Glennon RA, Dukat M, Grella B, Hong S,
  36. Costantino L Teitler M, et al. Binding of betacarbolines
  37. and related agents at serotonin (5-HT
  38. (2) and 5-HT(1A)), dopamine (D(2)) and
  39. benzodiazepine
  40. receptors. Drug Alcohol Depend 2000; 60:
  41. -32.
  42. Gonzalez LE, Andrews N, File SE. 5-HT1A
  43. and benzodiazepine receptors in the basolateral
  44. amygdala modulate anxiety in the social
  45. interaction test, but not in the elevated plusmaze.
  46. Brain Res1996; 732: 145-153.
  47. Herraiz T, Chaparro C. Human monoamine
  48. oxidase is inhibited by tobacco smoke: betacarboline
  49. alkaloids act as potent and reversible
  50. inhibitors. Biochem Biophys Res Commun
  51. 14; 326:378-86.
  52. Hillberp C,Hapillon P, Effect of harmaline on
  53. anxiety related behavior in mice.Physiol Behav
  54. (2005) :164-167
  55. Janhunen S, Ahtee L. Differential nicotinic
  56. regulation of the nigrostriatal and mesolimbic
  57. dopaminergic pathways: implications for drug
  58. development. Neurosci Biobehav Rev 2007; 31:
  59. -314.
  60. Le Doux J. The emotional brain, fear, and the
  61. amygdala. Cell Mol Neurobiol 2003; 23:727-
  62. Liebsch G, Landgraf R, Gerstberger R, et al.
  63. Chronic infusion of a CRH receptor
  64. antisenseoligodeoxynucleotide into the central
  65. nucleus of the amygdala reduced anxietyrelated
  66. behavior insocially defeated rats.
  67. Regulatory peptides, 1995; 59: 229-239.
  68. Masse F, Hascoet M, Dailly E, Bourin M.
  69. Effectof noradrenergic system on the
  70. anxiolytic-like effectof DOI (5-HT2A/2C
  71. agonists) in the four-plate
  72. test.Psychopharmacology (Berl) 2006;
  73. (4):471-81.
  74. Pandaranandaka J, Poonyachoti S,
  75. Kalandakanond-Thongsong S. Anxiolytic
  76. property of estrogen related to the changes of
  77. the monoamine levels in various brain regions
  78. of ovariectomizedrats. Physiol Behav 2006;
  79. (4):828-35.
  80. Pellow S. File SE. Anxiolytic and
  81. AnxiogenicDrug Effects on Exploratory
  82. Activity in an Elevated Plus-Maze: a Novel
  83. Test of Anxiety in the Rat.Pharmacol. Biochem
  84. Behav 986;24:525-529.
  85. Pfau W, Skog K. Exposure to beta-carbolines
  86. norharman and harman. J Chromatogr B
  87. AnalytTechnol Biomed Life Sci 2004; 802:115-
  88. Picentini MP,Piatti E,franternale D,Ricci
  89. D,Assorsi A.Phospholipase C-dependent
  90. phosphor-inositide break down induced by EIFEMP
  91. in peganum harmala call.Biochem
  92. ;86( 5):343-9
  93. Poorthuis RB, Goriounova NA, Couey JJ,
  94. Mansvelder HD. Nicotinic actions on
  95. neuronalnetworks for cognition: general
  96. principles and long-term consequences.
  97. Biochem Pharmacol 2009;78: 668-76.
  98. Rezayat M, Roohbakhsh A, Zarrindast MR,
  99. Massoudi R,Djahanguiri B. Cholecystokinin
  100. and GABA interaction in the dorsal
  101. hippocampus of rats in the elevated plus-maze
  102. test of anxiety.
  103. Physiology and behavior 2005; 84: 775-782.
  104. Sharaf EL, Ansari MA, Martin four flavonoide
  105. glycosidesfrom peganum harmala
  106. Phytochemistry 44(1997) 533-536.
  107. Spijkerman R, van den Eijnden R, van de
  108. Mheen D, Bongers I, Fekkes D. The impact of
  109. smoking and drinking on plasma levels of
  110. norharman. Eur Neuropsychopharmacol 2002;
  111. (1): 61-71
  112. Squires PE, Hills CE, Rogers GJ, Garland P,
  113. Farley SR, Morgan NG.The putative
  114. imidazoline receptor agonist, harmane,
  115. promotes intracellular calcium mobilisation in
  116. pancreatic beta-cells. Eur
  117. J Pharmacol 2004; 501: 31-9.
  118. Walker DL, Toufexis DJ, Davis M. Rote ofthe
  119. Bed Nucleus of the Stria Terminalis Versus the
  120. Amygdala in Fear, Stress and Anxiety. Eur
  121. JPharmacol 2003; 463:199-216.
  122. Zarrindast MR, Homayoun H, Babaie A,
  123. Etminani A, Gharib B. Involvement of
  124. adrenergic and cholinergic systems in nicotineinduced
  125. anxiogenesis in mice. Eur J Pharmacol
  126. ; 407: 145-15
  127. Zarrindast M, Solati J, Oryan S, Parivar K.
  128. Effect of Intra-Amygdala Injection of Nicotine
  129. and GABA Receptor Agents on Anxiety-Like
  130. Behavior in Rats. Pharmacology 2008; 82: 276-
  131. Zarrindast MR, Torabi M, Rostami P, Fazli-
  132. Tabaei S. The effects of histaminergic agents in
  133. the dorsal hippocampus of rats in the elevated
  134. plus-maze test of anxiety. Pharmacology,
  135. biochemistry, and behavior 2006; 85: 500-506.
  136. Pidoplichko VI, Noguchi J, Areola OO, Liang
  137. Y, Peterson J, Zhang T, et al. Nicotine
  138. cholinergic Synaptic mechanisms in the ventral
  139. tegmental area contribute to nicotine
  140. addiction.Learn Mem,2004;11( 1):60-9