SIMULTANEOUS MEASUREMENT OF OPIATE-INDUCED HISTAMINE-RELEASE IN THE PERIAQUEDUCTAL GRAY AND OPIATE ANTINOCICEPTION - AN IN-VIVO MICRODIALYSIS STUDY

Histamine release and the subsequent activation of H-2 receptors in th e periaqueductal gray (PAG) are thought to be important components of morphine antinociception. In vivo microdialysis and antinociceptive te sting were simultaneously applied in rats to characterize the effects of morphine on PAG histamine release and determine the relationship be tween histamine release and antinociception. In the absence of nocicep tive (tail pinch) testing, morphine (12.8 mg/kg) induced a delayed, lo ng-lasting release of histamine in the PAG. This effect of morphine wa s abolished by the opiate antagonist naltrexone (1 mg/kg) but was not mimicked by the mu-preferring agonist fentanyl (0.3 mg/kg), suggesting that activation of an opiate receptor other than, or in addition to, the mu receptor is necessary. In contrast to the findings with fentany l in untested animals, fentanyl combined with nociceptive testing incr eased histamine release, even though testing alone had no such effect. Unexpectedly, tail pinch testing inhibited morphine-induced histamine release. These results show that the test procedure alters the action of opiates on histamine release, an effect likely to be the result of the stress of repeated tail pinch testing. Therefore, although histam ine release may not be obligatory for all types of opiate antinocicept ion, histamine in the PAG may function as a mediator of stress-induced potentiation of opiate antinociception. Even though the microdialysis technique has been acclaimed for its ability to assess neurochemical and behavioral characteristics simultaneously, the introduction of noc iceptive testing clearly can alter the neurochemical systems under stu dy.