Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats

Ann Agric Environ Med. 2021 Sep 16;28(3):437-445. doi: 10.26444/aaem/126020. Epub 2020 Oct 20.

Abstract

Introduction: Dihydroergotamine (DHE) is a derivative of an ergot alkaloid used as an antimigraine medication. Nowadays, ergot alkaloids may still endanger the safety of humans and animals as food or medicine pollutants, but the outcomes of long-term DHE administration on the behaviour and neurotransmission remain undescribed.

Material and methods: Adult male Wistar Albino Glaxo rats pre-treated orally with DHE for six weeks were investigated to assess the relationship between concentration of neurotransmitters and behavioural response. The behavioural effects of the drug administered at doses of either 30 µg/kg b.w. (group DHE30, n = 11) or 100 µg/kg b.w. per day (group DHE100, n = 10) were evaluated in the Morris Water Maze. It is known that monoaminergic neurotransmitters (serotonin, noradrenaline and dopamine) in some brain structures (prefrontal cortex, hippocampus, striatum, cerebellum, spinal cord) play a role in the control of cognitive and motor functions. The concentration of neurotransmitters was determined by High Performance Liquid Chromatography (HPLC).

Results: Administration of DHE influenced neither the learning processes nor memory in rats. Nevertheless, an increased motor activity of the DHE-administered animals was observed in both the cued and non-cued behavioural tasks. In HPLC examination, changes in the concentration of monoaminergic neurotransmitters and their metabolites were noted in all tested structures, except for the hippocampus.

Conclusions: DHE is able to modulate noradrenergic, serotonergic and dopaminergic neurotransmission that may support the increase in locomotion.

Keywords: Neurotransmission; behavior; brain; dihydroergotamine; ergot derivatives; memory; rats.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Dihydroergotamine / administration & dosage*
  • Dopamine / metabolism
  • Learning
  • Male
  • Memory / drug effects
  • Morris Water Maze Test
  • Neurotransmitter Agents / metabolism
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Spatial Behavior / drug effects*
  • Synaptic Transmission / drug effects

Substances

  • Neurotransmitter Agents
  • Serotonin
  • Dihydroergotamine
  • Dopamine