Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat

Behav Brain Res. 2008 Jan 10;186(1):98-106. doi: 10.1016/j.bbr.2007.07.036. Epub 2007 Aug 2.

Abstract

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxytryptamine / administration & dosage
  • 5-Methoxytryptamine / physiology*
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Anxiety / etiology
  • Anxiety / metabolism
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism
  • Drug Synergism
  • Ergolines / pharmacology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Female
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Piperazines / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin Agents / pharmacology
  • Sex Factors
  • Statistics, Nonparametric
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism

Substances

  • Ergolines
  • Piperazines
  • Pyridines
  • Serotonin Agents
  • Receptor, Serotonin, 5-HT1A
  • LY 178210
  • 5-Methoxytryptamine
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide