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School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand
The influence of µ-selective opioid agonists on neonatal thermoregulatory mechanisms has received little attention. Opioid treatment in adult subjects can cause either hyper- or hypothermia, depending on the experimental conditions, the strain of rat used, and the dose and route of administration of the drug. The present study assessed the effect of two µ opioid agonists on body temperature in neonatal Wistar rats aged 2 to 13 days. Rat pups were administered either saline or one of the two µ-selective opioid agonists, dermorphin (0.4 mg/kg) or fentanyl (0.06 mg/kg), by subcutaneous injection. Continuous rectal temperatures were measured both prior to and following drug or saline injection in freely moving, conscious animals. Ambient temperature in a plethysmograph chamber was maintained within or close to the thermoneutral zone for pups (32°C). To distinguish between µ-1 and µ-2 effects, all animals received either saline or 10 mg/kg of the irreversible µ-1 antagonist naloxonazine (NALZ) 1 day prior to agonist administration. NALZ on its own had no effect on body temperature. Dermorphin and fentanyl both caused a fall in body temperature in pups of all age groups. The temperature decreases ranged from 0.8°-2.2°C. These opioid-induced changes were inhibited by NALZ pretreatment. Although there was no evidence for endogenous µ-1 opioid activity, this study indicated that stimulation of µ-1 opioid receptors causes a decrease in body temperature in conscious, unrestrained neonatal rats under or close to thermoneutral conditions.
Key Words: dermorphin fentanyl µ-1 naloxonazine neonate opioid rat thermoregulation
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