Vertical exposition to Luffa operculata extract deregulates behavior and hypothalamus neurotransmitters in juvenile rats

J Ethnopharmacol. 2021 Jan 10:264:113265. doi: 10.1016/j.jep.2020.113265. Epub 2020 Aug 25.

Abstract

Ethnopharmacological relevance: Luffa operculata (L.) Cogn (Cucurbitaceae) is a traditional plant popularly used in the abortion induction, against sinusitis and is toxic.

Aim of the study: To verify the influence of the aqueous extract obtained from the dry fruit of L. operculata (BNE) on the male rats vertically exposed to a subabortive dose of BNE, by evaluating alterations in behavior and neurochemical features in hypothalamus, striatum and frontal cortex, at a juvenile age, after receiving a stress challenge given by the use of the "New York subway stress" technique (NYS).

Materials and methods: Pregnant female rats (F0 generation) received 1.0 mg/kg BNE, or distilled water (100 mL/kg), by gavage, between gestation days GD17 and GD21. The pups were weaned at PND21 and were kept up to PND60 (juvenile age) in controlled environmental conditions. Four groups were obtained: control (CG), experimental (EG), stress control (SCG) and stress experimental (SEG) After being stressed, the animals were behavioral screened for in the open field (OF) and in light-dark box (LDB) apparatuses. They were euthanized, and the liver, kidneys and brain were removed for both macroscopic and microscopic analyses, and for quantification of vanillylmandelic acid (VMA), norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the serotonin (5-HT) and its metabolite 5-hydroxyindolylacetic acid (5-HIAA) were accessed in the hypothalamus, frontal cortex and striatum.

Results and discussion: although most of the behavior changes were due to the stress challenge, the rats spent more time in the dark side of the LDB and were less likely to explore the light side, indicating that the treatment with BNE induced to fear. Interferences of BNE over behavior were due to impairment of VMA, NE, 5-HT and DA and increasing of DOPAC in the hypothalamus, and an increase of 5-HIAA in the frontal cortex, indicating alterations in the hypothalamic-hypophysis-adrenal axis (HHAA). No macroscopic or histopathological changes were observed in the liver, kidneys, or brain, although GFAP was diminished in the SCG, as expected for stressed rats.

Conclusion: the vertical exposition of juvenile rats to BNE led to the manifestation of fear and to a down regulation of the hypothalamic-hypophysis-adrenal axis.

Keywords: Animal behavior; Buchinha-do-norte; Cognitive performance; Light-dark box; Neurochemistry; Open field; Prenatal exposition; Toxicology; Traditional medicine meso- and Southern America.

MeSH terms

  • Age Factors
  • Animals
  • Dopamine / metabolism
  • Fear / drug effects*
  • Fear / physiology
  • Fear / psychology
  • Female
  • Hydroxyindoleacetic Acid / metabolism
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism*
  • Luffa*
  • Male
  • Neurotransmitter Agents / metabolism*
  • Plant Extracts / administration & dosage*
  • Plant Extracts / isolation & purification
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / metabolism*
  • Prenatal Exposure Delayed Effects / psychology
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism

Substances

  • Neurotransmitter Agents
  • Plant Extracts
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Dopamine