Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice

PLoS One. 2014 Dec 22;9(12):e114869. doi: 10.1371/journal.pone.0114869. eCollection 2014.

Abstract

During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Animals
  • Clonidine / pharmacology*
  • Female
  • Male
  • Memory, Short-Term / drug effects*
  • Mice
  • Motor Activity / drug effects
  • Pain Management
  • Reflex, Startle / drug effects
  • Vestibular Nerve / drug effects
  • Vestibular Nerve / growth & development

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Clonidine

Grant support

This work was supported by Spanish BFU2007-67173 grant and the Fundación Conocimiento y Cultura. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.