Cellular and Molecular Life Sciences

, Volume 67, Issue 14, pp 2467–2479 | Cite as

Characterization of the 5-HT1A receptor of the honeybee (Apis mellifera) and involvement of serotonin in phototactic behavior

  • Markus Thamm
  • Sabine Balfanz
  • Ricarda Scheiner
  • Arnd Baumann
  • Wolfgang BlenauEmail author
Research Article


Serotonin plays a key role in modulating various physiological and behavioral processes in both protostomes and deuterostomes. The vast majority of serotonin receptors belong to the superfamily of G-protein-coupled receptors. We report the cloning of a cDNA from the honeybee (Am5-ht1A) sharing high similarity with members of the 5-HT1 receptor class. Activation of Am5-HT1A by serotonin inhibited the production of cAMP in a dose-dependent manner (EC50 = 16.9 nM). Am5-HT1A was highly expressed in brain regions known to be involved in visual information processing. Using in vivo pharmacology, we could demonstrate that Am5-HT1A receptor ligands had a strong impact on the phototactic behavior of individual bees. The data presented here mark the first comprehensive study—from gene to behavior—of a 5-HT1A receptor in the honeybee, paving the way for the eventual elucidation of additional roles of this receptor subtype in the physiology and behavior of this social insect.


5-HT Biogenic amine Cyclic AMP GPCR Phototaxis Signal transduction 









Antibody diluent


Apis mellifera 5-HT1A receptor


Gene or cDNA encoding Apis mellifera 5-HT1A receptor


Intracellular cAMP level


Central nervous system


Third cytoplasmic loop


Hemagglutinin A

HEK 293

Human embryonic kidney cells


Phosphate-buffered saline


Tris-buffered saline containing Tween 20


Transmembrane domain



We thank J. Schlenstedt for initiating the work on the honeybee 5-HT1A receptor and J. Erber for supporting the phototaxis experiments. This work was supported by the German Science Foundation (Research Training Group 837 Functional Insect Science, scholarship to M.T.).


  1. 1.
    Weiger WA (1997) Serotonergic modulation of behaviour: a phylogenetic overview. Biol Rev Camb Philos Soc 72:61–95CrossRefPubMedGoogle Scholar
  2. 2.
    Jones BJ, Blackburn TP (2002) The medical benefit of 5-HT research. Pharmacol Biochem Behav 71:555–568CrossRefPubMedGoogle Scholar
  3. 3.
    Walz B, Baumann O, Krach C, Baumann A, Blenau W (2006) The aminergic control of cockroach salivary glands. Arch Insect Biochem Physiol 62:141–152CrossRefPubMedGoogle Scholar
  4. 4.
    Colas JF, Launay JM, Kellermann O, Rosay P, Maroteaux L (1995) Drosophila 5-HT2 serotonin receptor: coexpression with fushi-tarazu during segmentation. Proc Natl Acad Sci USA 92:5441–5445CrossRefPubMedGoogle Scholar
  5. 5.
    Yuan Q, Lin F, Zheng X, Sehgal A (2005) Serotonin modulates circadian entrainment in Drosophila. Neuron 47:115–127CrossRefPubMedGoogle Scholar
  6. 6.
    Dierick HA, Greenspan RJ (2007) Serotonin and neuropeptide F have opposite modulatory effects on fly aggression. Nat Genet 39:678–682CrossRefPubMedGoogle Scholar
  7. 7.
    Anstey ML, Rogers SM, Ott SR, Burrows M, Simpson SJ (2009) Serotonin mediates behavioral gregarization underlying swarm formation in desert locusts. Science 323:627–630CrossRefPubMedGoogle Scholar
  8. 8.
    Sitaraman D, Zars M, Laferriere H, Chen YC, Sable-Smith A, Kitamoto T, Rottinghaus GE, Zars T (2008) Serotonin is necessary for place memory in Drosophila. Proc Natl Acad Sci USA 105:5579–5584CrossRefPubMedGoogle Scholar
  9. 9.
    Taylor DJ, Robinson GE, Logan BJ, Laverty R, Mercer AR (1992) Changes in brain amine levels associated with the morphological and behavioural development of the worker honeybee. J Comp Physiol A 170:715–721CrossRefPubMedGoogle Scholar
  10. 10.
    Wagener-Hulme C, Kuehn JC, Schulz DJ, Robinson GE (1999) Biogenic amines and division of labor in honey bee colonies. J Comp Physiol A 184:471–479CrossRefPubMedGoogle Scholar
  11. 11.
    Schulz DJ, Robinson GE (1999) Biogenic amines and division of labor in honey bee colonies: behaviorally related changes in the antennal lobes and age-related changes in the mushroom bodies. J Comp Physiol A 184:481–488CrossRefPubMedGoogle Scholar
  12. 12.
    Schürmann FW, Klemm N (1984) Serotonin-immunoreactive neurons in the brain of the honeybee. J Comp Neurol 225:570–580CrossRefPubMedGoogle Scholar
  13. 13.
    Seidel C, Bicker G (1996) The developmental expression of serotonin-immunoreactivity in the brain of the pupal honeybee. Tissue Cell 28:663–672CrossRefPubMedGoogle Scholar
  14. 14.
    Bicker G, Menzel R (1989) Chemical codes for the control of behaviour in arthropods. Nature 337:33–39CrossRefPubMedGoogle Scholar
  15. 15.
    Menzel R, Heyne A, Kinzel C, Gerber B, Fiala A (1999) Pharmacological dissociation between the reinforcing, sensitizing, and response-releasing functions of reward in honeybee classical conditioning. Behav Neurosci 113:744–754CrossRefPubMedGoogle Scholar
  16. 16.
    Hannon J, Hoyer D (2008) Molecular biology of 5-HT receptors. Behav Brain Res 195:198–213CrossRefPubMedGoogle Scholar
  17. 17.
    Nichols DE, Nichols CD (2008) Serotonin receptors. Chem Rev 108:1614–1641CrossRefPubMedGoogle Scholar
  18. 18.
    Blenau W, Baumann A (2001) Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera. Arch Insect Biochem Physiol 48:13–38CrossRefPubMedGoogle Scholar
  19. 19.
    Hauser F, Cazzamali G, Williamson M, Blenau W, Grimmelikhuijzen CJ (2006) A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera. Prog Neurobiol 80:1–19CrossRefPubMedGoogle Scholar
  20. 20.
    Saudou F, Boschert U, Amlaiky N, Plassat JL, Hen R (1992) A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J 11:7–17PubMedGoogle Scholar
  21. 21.
    Witz P, Amlaiky N, Plassat JL, Maroteaux L, Borrelli E, Hen R (1990) Cloning and characterization of a Drosophila serotonin receptor that activates adenylate cyclase. Proc Natl Acad Sci USA 87:8940–8944CrossRefPubMedGoogle Scholar
  22. 22.
    Blenau W, Erber J, Baumann A (1998) Characterization of a dopamine D1 receptor from Apis mellifera: cloning, functional expression, pharmacology, and mRNA localization in the brain. J Neurochem 70:15–23PubMedCrossRefGoogle Scholar
  23. 23.
    Blenau W, Balfanz S, Baumann A (2000) Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor. J Neurochem 74:900–908CrossRefPubMedGoogle Scholar
  24. 24.
    Grohmann L, Blenau W, Erber J, Ebert PR, Strünker T, Baumann A (2003) Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain. J Neurochem 86:725–735CrossRefPubMedGoogle Scholar
  25. 25.
    Mustard JA, Blenau W, Hamilton IS, Ward VK, Ebert PR, Mercer AR (2003) Analysis of two D1-like dopamine receptors from the honey bee Apis mellifera reveals agonist-independent activity. Brain Res Mol Brain Res 113:67–77CrossRefPubMedGoogle Scholar
  26. 26.
    Beggs KT, Hamilton IS, Kurshan PT, Mustard JA, Mercer AR (2005) Characterization of a D2-like dopamine receptor (AmDOP3) in honey bee, Apis mellifera. Insect Biochem Mol Biol 35:873–882CrossRefPubMedGoogle Scholar
  27. 27.
    Beggs KT, Mercer AR (2009) Dopamine receptor activation by honey bee queen pheromone. Curr Biol 19:1206–1209CrossRefPubMedGoogle Scholar
  28. 28.
    Schlenstedt J, Balfanz S, Baumann A, Blenau W (2006) Am5-HT7: molecular and pharmacological characterization of the first serotonin receptor of the honeybee (Apis mellifera). J Neurochem 98:1985–1998CrossRefPubMedGoogle Scholar
  29. 29.
    Troppmann B, Balfanz S, Baumann A, Blenau W (2010) Inverse agonist and neutral antagonist actions of synthetic compounds at an insect 5-HT1 receptor. Br J Pharmacol. doi: 10.1111/j.1476-5381.2010.00638.x
  30. 30.
    Erber J, Hoormann J, Scheiner R (2006) Phototactic behaviour correlates with gustatory responsiveness in honey bees (Apis mellifera L.). Behav Brain Res 174:174–180CrossRefPubMedGoogle Scholar
  31. 31.
    Käll L, Krogh A, Sonnhammer EL (2004) A combined transmembrane topology and signal peptide prediction method. J Mol Biol 338:1027–1036CrossRefPubMedGoogle Scholar
  32. 32.
    Moro O, Lameh J, Högger P, Sadée W (1993) Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. J Biol Chem 268:22273–22276PubMedGoogle Scholar
  33. 33.
    Barak LS, Tiberi M, Freedman NJ, Kwatra MM, Lefkowitz RJ, Caron MG (1994) A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated β2-adrenergic receptor sequestration. J Biol Chem 269:2790–2795PubMedGoogle Scholar
  34. 34.
    Schäfer S, Bicker G (1986) Common projection areas of 5-HT- and GABA-like immunoreactive fibers in the visual system of the honeybee. Brain Res 380:368–370CrossRefPubMedGoogle Scholar
  35. 35.
    Ehmer B, Gronenberg W (2002) Segregation of visual input to the mushroom bodies in the honeybee (Apis mellifera). J Comp Neurol 451:362–373CrossRefPubMedGoogle Scholar
  36. 36.
    Erber J, Kloppenburg P, Scheidler A (1993) Neuromodulation by serotonin and octopamine in the honeybee: behaviour, neuroanatomy and electrophysiology. Experientia 49:1073–1083CrossRefGoogle Scholar
  37. 37.
    Erber J, Kloppenburg P (1995) The modulatory effects of serotonin and octopamine in the visual system of the honey bee (Apis mellifera L.). I. Behavioral analysis of the motion-sensitive antennal reflex. J Comp Physiol A 176:111–118CrossRefGoogle Scholar
  38. 38.
    Kloppenburg P, Erber J (1995) The modulatory effects of serotonin and octopamine in the visual system of the honey bee (Apis mellifera L.). II. Electrophysiological analysis of motion-sensitive neurons in the lobula. J Comp Physiol A 176:119–129CrossRefGoogle Scholar
  39. 39.
    Müller U (1997) Neuronal cAMP-dependent protein kinase type II is concentrated in mushroom bodies of Drosophila melanogaster and the honeybee Apis mellifera. J Neurobiol 33:33–44CrossRefPubMedGoogle Scholar
  40. 40.
    Blenau W, Erber J (1998) Behavioural pharmacology of dopamine, serotonin and putative aminergic ligands in the mushroom bodies of the honeybee (Apis mellifera). Behav Brain Res 96:115–124CrossRefPubMedGoogle Scholar
  41. 41.
    Kroeze WK, Kristiansen K, Roth BL (2002) Molecular biology of serotonin receptors structure and function at the molecular level. Curr Top Med Chem 2:507–528CrossRefPubMedGoogle Scholar
  42. 42.
    Olde B, McCombie WR (1997) Molecular cloning and functional expression of a serotonin receptor from Caenorhabditis elegans. J Mol Neurosci 8:53–62CrossRefPubMedGoogle Scholar
  43. 43.
    Barbas D, Zappulla JP, Angers S, Bouvier M, Castellucci VF, DesGroseillers L (2002) Functional characterization of a novel serotonin receptor (5-HTap2) expressed in the CNS of Aplysia californica. J Neurochem 80:335–345CrossRefPubMedGoogle Scholar
  44. 44.
    Chen A, Holmes SP, Pietrantonio PV (2004) Molecular cloning and functional expression of a serotonin receptor from the Southern cattle tick, Boophilus microplus (Acari: Ixodidae). Insect Mol Biol 13:45–54CrossRefPubMedGoogle Scholar
  45. 45.
    Spitzer N, Edwards DH, Baro DJ (2008) Conservation of structure, signaling and pharmacology between two serotonin receptor subtypes from decapod crustaceans, Panulirus interruptus and Procambarus clarkii. J Exp Biol 211:92–105CrossRefPubMedGoogle Scholar
  46. 46.
    Nichols CD, Ronesi J, Pratt W, Sanders-Bush E (2002) Hallucinogens and Drosophila: linking serotonin receptor activation to behavior. Neuroscience 115:979–984CrossRefPubMedGoogle Scholar
  47. 47.
    Johnson O, Becnel J, Nichols CD (2009) Serotonin 5-HT2 and 5-HT1A-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster. Neuroscience 158:1292–1300CrossRefPubMedGoogle Scholar
  48. 48.
    Yuan Q, Joiner WJ, Sehgal A (2006) A sleep-promoting role for the Drosophila serotonin receptor 1A. Curr Biol 16:1051–1062CrossRefPubMedGoogle Scholar
  49. 49.
    Heisenberg M (2003) Mushroom body memoir: from maps to models. Nat Rev Neurosci 4:66–75CrossRefGoogle Scholar
  50. 50.
    Giurfa M (2006) Associative learning: the instructive function of biogenic amines. Curr Biol 16:R892–R895CrossRefPubMedGoogle Scholar
  51. 51.
    Giurfa M (2007) Behavioral and neural analysis of associative learning in the honeybee: a taste from the magic well. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 193:801–824CrossRefPubMedGoogle Scholar
  52. 52.
    Schwärzel M, Müller U (2006) Dynamic memory networks: dissecting molecular mechanisms underlying associative memory in the temporal domain. Cell Mol Life Sci 63:989–998CrossRefPubMedGoogle Scholar
  53. 53.
    Berry J, Krause WC, Davis RL (2008) Olfactory memory traces in Drosophila. Prog Brain Res 169:293–304CrossRefPubMedGoogle Scholar
  54. 54.
    Mercer AR (2008) A bee-line into learning and memory mechanisms. Cell Mol Life Sci 65:3521–3524CrossRefPubMedGoogle Scholar
  55. 55.
    Müller U (2000) Prolonged activation of cAMP-dependent protein kinase during conditioning induces long-term memory in honeybees. Neuron 27:159–168CrossRefPubMedGoogle Scholar
  56. 56.
    Page RE Jr, Erber J (2002) Levels of behavioral organization and the evolution of division of labor. Naturwissenschaften 89:91–106CrossRefPubMedGoogle Scholar
  57. 57.
    Scheiner R, Baumann A, Blenau W (2006) Aminergic control and modulation of honeybee behaviour. Curr Neuropharmacol 4:259–276CrossRefPubMedGoogle Scholar
  58. 58.
    Mercer AR, Mobbs PG, Davenport AP, Evans PD (1983) Biogenic amines in the brain of the honeybee, Apis mellifera. Cell Tissue Res 234:655–677CrossRefPubMedGoogle Scholar
  59. 59.
    Rodriguez Moncalvo VG, Campos AR (2009) Role of serotonergic neurons in the Drosophila larval response to light. BMC Neurosci 10:66CrossRefPubMedGoogle Scholar
  60. 60.
    Rodríguez-Sosa L, Calderón-Rosete G, Flores G, Porras MG (2007) Serotonin-caused phase shift of circadian rhythmicity in a photosensitive neuron. Synapse 61:801–808CrossRefPubMedGoogle Scholar
  61. 61.
    Calderón-Rosete G, Flores G, Rodríguez-Sosa L (2006) Diurnal rhythm in the levels of the serotonin 5-HT1A receptors in the crayfish eyestalk. Synapse 59:368–373CrossRefPubMedGoogle Scholar
  62. 62.
    Claridge-Chang A, Wijnen H, Naef F, Boothroyd C, Rajewsky N, Young MW (2001) Circadian regulation of gene expression systems in the Drosophila head. Neuron 32:657–671CrossRefPubMedGoogle Scholar
  63. 63.
    Moore D, Angel JE, Cheeseman IM, Fahrbach SE, Robinson GE (1998) Timekeeping in the honey bee colony: integration of circadian rhythms and division of labor. Behav Ecol Sociobiol 43:147–160CrossRefGoogle Scholar
  64. 64.
    Bloch G, Robinson GE (2001) Reversal of honeybee behavioural rhythms. Nature 410:1048CrossRefPubMedGoogle Scholar
  65. 65.
    Honeybee Genome Sequencing Consortium (2006) Insights into social insects from the genome of the honeybee Apis mellifera. Nature 443:931–949CrossRefGoogle Scholar
  66. 66.
    Page RE Jr, Scheiner R, Erber J, Amdam GV (2006) The development and evolution of division of labor and foraging specialization in a social insect (Apis mellifera L.). Curr Top Dev Biol 74:253–286CrossRefPubMedGoogle Scholar

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Markus Thamm
    • 1
  • Sabine Balfanz
    • 2
  • Ricarda Scheiner
    • 1
  • Arnd Baumann
    • 2
  • Wolfgang Blenau
    • 1
    Email author
  1. 1.Institute of Biochemistry and Biology, Animal PhysiologyUniversity of PotsdamPotsdamGermany
  2. 2.Institute of Structural Biology and Biophysics 1Forschungszentrum JülichJülichGermany

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