Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice

Fundam Clin Pharmacol. 2016 Feb;30(1):4-13. doi: 10.1111/fcp.12165. Epub 2015 Nov 23.


Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration.

Keywords: adipokinetic hormone; animal behavior; mice; neurogenesis; neurotrophic factors.

MeSH terms

  • Analgesics / isolation & purification
  • Analgesics / pharmacology
  • Animals
  • Anti-Anxiety Agents / isolation & purification
  • Anti-Anxiety Agents / pharmacology
  • Behavior, Animal / drug effects*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Insect Hormones / isolation & purification
  • Insect Hormones / pharmacology*
  • Maze Learning / drug effects
  • Mice, Inbred Strains
  • Motor Activity / drug effects
  • Neurogenesis / drug effects*
  • Neuropeptides / isolation & purification
  • Neuropeptides / pharmacology*
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology
  • Oligopeptides / isolation & purification
  • Oligopeptides / pharmacology*
  • Pyrrolidonecarboxylic Acid / analogs & derivatives*
  • Pyrrolidonecarboxylic Acid / isolation & purification
  • Pyrrolidonecarboxylic Acid / pharmacology
  • Swimming


  • Analgesics
  • Anti-Anxiety Agents
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Insect Hormones
  • Neuropeptides
  • Neuroprotective Agents
  • Oligopeptides
  • adipokinetic hormone
  • hypertrehalosemic hormone
  • Pyrrolidonecarboxylic Acid