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ANESTHETIC PHARMACOLOGY

The Effect of Meperidine on Thermoregulation in Mice: Involvement of ₂-Adrenoceptors

Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; *Department of Anesthesia, University of California, San Francisco, California

Address correspondence to Andrea Paris, MD, Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel Schwanenweg 21, D-24105 Kiel, Germany. Address e-mail to paris{at}anaesthesie.uni-kiel.de

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that ₂-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific ₂-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6°C ± 0.7°C) versus saline (37.9°C ± 0.6°C) and versus atipamezole plus saline (37.8°C ± 0.4°C; P < 0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7°C ± 0.6°C; P < 0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of ₂-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.

IMPLICATIONS: Meperidine decreases the threshold for nonshivering thermogenesis in mice. This effect was abolished by administration of the ₂-adrenoceptor antagonist atipamezole, suggesting a predominant role of ₂-adrenoceptors in the inhibition of thermoregulation by meperidine. This model of thermoregulation in mice may be useful to further elucidate general mechanisms of thermoregulation.

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