1-Oleoyl lysophosphatidic acid: a new mediator of emotional behavior in rats

PLoS One. 2014 Jan 7;9(1):e85348. doi: 10.1371/journal.pone.0085348. eCollection 2014.

Abstract

The role of lysophosphatidic acid (LPA) in the control of emotional behavior remains to be determined. We analyzed the effects of the central administration of 1-oleoyl-LPA (LPA 18∶1) in rats tested for food consumption and anxiety-like and depression-like behaviors. For this purpose, the elevated plus-maze, open field, Y maze, forced swimming and food intake tests were performed. In addition, c-Fos expression in the dorsal periaqueductal gray matter (DPAG) was also determined. The results revealed that the administration of LPA 18∶1 reduced the time in the open arms of the elevated plus-maze and induced hypolocomotion in the open field, suggesting an anxiogenic-like phenotype. Interestingly, these effects were present following LPA 18∶1 infusion under conditions of novelty but not under habituation conditions. In the forced swimming test, the administration of LPA 18∶1 dose-dependently increased depression-like behavior, as evaluated according to immobility time. LPA treatment induced no effects on feeding. However, the immunohistochemical analysis revealed that LPA 18∶1 increased c-Fos expression in the DPAG. The abundant expression of the LPA1 receptor, one of the main targets for LPA 18∶1, was detected in this brain area, which participates in the control of emotional behavior, using immunocytochemistry. These findings indicate that LPA is a relevant transmitter potentially involved in normal and pathological emotional responses, including anxiety and depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Behavior, Animal* / drug effects
  • Emotions / drug effects
  • Emotions / physiology*
  • Feeding Behavior / drug effects
  • Lysophospholipids / metabolism*
  • Lysophospholipids / pharmacology
  • Male
  • Maze Learning / drug effects
  • Motor Activity / drug effects
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Receptors, Lysophosphatidic Acid / metabolism

Substances

  • Lysophospholipids
  • Proto-Oncogene Proteins c-fos
  • Receptors, Lysophosphatidic Acid
  • lysophosphatidic acid

Grants and funding

The present study was supported through funding from the Instituto de Salud Carlos III, Red de Trastornos Adictivos UE-FEDER RD06/0001/0000 and RD12/0028/0001 (F.R.d.F. and F.J.P.), Ministerio de Ciencia e Innovación SEJ2007-61187 and PSI2010-16160 (L.J.S.), and SAF2010-20521 (F.R.d.F.), I3SNS Programme (G.E.O.), and Consejería de Economía, Innovación y Ciencia, Junta de Andalucía (grants CTS-433 and CTS-065). E.C.O. received a ‘Sara Borrell’ fellowship from the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.