THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Copyright © i988 by The American Society for Pharmacology and Experimental Therapeutics Cross-Tolerance and Cross-Sensitization between Morphine

Recent studies have shown that different regimens of footshock elicit either “opiate ” (naloxone-sensitive) or “histaminergic ” (ci-metidine-sensitive but naloxone-insensitive) analgesic re-sponses. Presently, the nature of these responses was further investigated by characterizing the development of tolerance to these stress paradigms and by assessing the degree of cross-tolerance between these treatments and morphine (MOR) in rats. Daily exposure to the “opiate ” stress paradigm for 7 days re-suIted in a significant loss of this form of footshock-induced analgesia (FSIA), but the same exposure to the “histaminergic” regimen resulted in no such tolerance. One day later, animals from the “opiate”-stressed group exhibited MOR analgesia that was comparable to that in unstressed animals, whereas animals chronically exposed to the “histaminergic ” paradigm showed highly potentiated responses to MOR. However, when naiv