Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood

Paediatr Anaesth. 2012 Jul;22(7):713-9. doi: 10.1111/j.1460-9592.2012.03810.x. Epub 2012 Feb 6.

Abstract

Background and objective: The use of dexmedetomidine (DEX), a selective alpha-2 agonist, in pediatric practice is expanding as a result of its desirable properties. To clarify the long-term neurological consequences of neonatal administration of DEX, we investigated the long-term effects of neonatal administration of DEX on hippocampal synaptic activity.

Methods: The rat pups received a bolus intraperitoneal injection of either 5 or 10 μg·kg(-1) DEX, or an equivalent volume of vehicle on postnatal day 7 (P7). Nine weeks after administration, evoked potentials (population spike, PS) and long-term potentiation (LTP) in the hippocampal CA1 region of rats were studied in vivo.

Results: Dexmedetomidine had a considerable sedative effect at these doses with little respiratory depression on P7. Nine weeks after administration of DEX, the amplitude of PS in the two treated groups was similar to that in the control group. DEX-treated rats showed no impairment in the induction of LTP. Furthermore, the response in PS to the paired stimuli was not impaired by neonatal administration of DEX.

Conclusion: These findings demonstrate that a single administration of DEX to rats on P7 preserves hippocampal synaptic plasticity as well as synaptic transmission later in life. In view of the some evidence that have demonstrated the permanent detrimental impact of commonly used anesthetics on neurological outcomes after neonatal exposure, our findings may suggest the relative safety of DEX administered as a sedative agent to neonatal animals with regard to the development of hippocampal synaptic functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Animals, Newborn
  • Blood Gas Analysis
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • Dexmedetomidine / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophysiological Phenomena
  • Evoked Potentials / drug effects
  • Hippocampus / drug effects*
  • Long-Term Potentiation / drug effects
  • Male
  • Membrane Potentials
  • Neuronal Plasticity / drug effects*
  • Pyramidal Cells / drug effects
  • Rats
  • Rats, Wistar
  • Synapses / drug effects*
  • Synaptic Transmission / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Dexmedetomidine