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 micrograms/kg) elevated jump thresholds 60 min following injection. While clonidine (1000 micrograms/kg) paired with a 2 degrees C CWS potentiated CWS analgesia in a synergistic manner, additivity of analgesic effects was observed following pairing of clonidine (500 micrograms/kg) with a 2 degrees C CWS and pairing of clonidine (500 and 1000 micrograms/kg) with a 15 degrees C CWS. The second experiment showed that clonidine (500 micrograms/kg) paired with a 2 degrees C CWS enhanced CWS enhanced CWS analgesia on the tail-flick test. The third experiment indicated that while clonidine (500 and 1000 micrograms/kg) or CWS (2 degrees 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.