Telemetry monitoring for non-invasive assessment of changes in core temperature after spinal drug administration in freely moving rats

J Pharmacol Toxicol Methods. 2015 Mar-Apr:72:19-25. doi: 10.1016/j.vascn.2015.01.002. Epub 2015 Jan 14.

Abstract

Introduction: There are no data available about the effects of spinally administered drugs on thermoregulation in freely moving animals. The first goal of the present study was to throw light on the consequences of intrathecally administered saline as a vehicle on core temperature and motor activity in unrestrained conditions. The second goal was to characterize the effects of morphine on these parameters as a widely used antinociceptive drug in spinal anesthesia, and reveal the potential role of the N-methyl-d-aspartate (NMDA) receptors in these processes.

Methods: For these purposes, male Wistar rats were catheterized intrathecally, and E-Mitter battery-free transponders were implanted intraabdominally to continuously monitor core temperature and locomotor activity.

Results: Saline induced a short-lasting hyperactivity accompanied by significant and prolonged hyperthermia that was blunted by systemic paracetamol administration. Morphine had no impact on motor activity; however, it caused high but equivalent degree hyperthermia in a wide dose range (1-15 μg), suggesting that it reached its peak effect. In the highest applied dose (25 μg), the NMDA receptor antagonist kynurenic acid blunted the saline-induced hyperthermia, and all doses caused higher hyperactivity compared to vehicle or morphine injections. In combination, kynurenic acid significantly inhibited the morphine-induced hyperthermia.

Discussion: These data suggest that this method might be a valuable tool for investigating the thermoregulatory and locomotor effects of different drugs at spinal level; however, the prolonged effects of intrathecal vehicle injections should also be considered. The results point out that morphine is a very potent hyperthermic drug that may act primarily on the efferent limb of thermoregulation, at least partially, via an indirect NMDA-receptor mediated action mechanism.

Keywords: Core temperature; Freely moving; Intrathecal; Locomotor activity; Opioid; Spinal; Telemetry; Thermoregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology
  • Animals
  • Body Temperature / physiology*
  • Cross-Over Studies
  • Drug Therapy, Combination
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Injections, Spinal
  • Kynurenic Acid / administration & dosage
  • Kynurenic Acid / pharmacology*
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Rats
  • Rats, Wistar
  • Telemetry*

Substances

  • Analgesics, Opioid
  • Excitatory Amino Acid Antagonists
  • Morphine
  • Kynurenic Acid