Potentiation of cold-water swim analgesia and hypothermia by clonidine

The analgesia induced by acute exposure to cold- water swims (CWS) covaries with levels of brain norepinephrine and is reduced by lesions placed in the locus coeruleus. In assessing whether alpha-noradrenergic receptor mechanisms mediated CWS analgesia, the first experiment found that clonidine pretreatment (500, 1000 μg/kg) elevated jump thresholds 60 min following injection. While clonidine (1000 μg/kg) paired with a 2°C CWS potentiated CWS analgesia in a synergistic manner, additivity of analgesic effects was observed following pairing of clonidine (500 μg/kg) with a 2°C CWS and pairing of clonidine (500 and 1000 μ/kg) with a 15°C CWS. The second experiment showed that clonidine (500 μg/kg) paired with a 2°C CWS enhanced CWS analgesia on the tail-flick test. The third experiment indicated that while clonidine (500 and 1000 μg/kg) or CWS (2°C) each produced hypothermia, pairing of these clonidine doses with CWS enhanced CWS hypothermia. These data are discussed in terms of the possible modulatory role that norepinephrine, and particularly its alpha-noradrenergic receptor subclass, plays in the full expression of CWS analgesia and hypothermia.