Abstract
The present study examined the ability of a taste cue to serve as a conditioned stimulus (CS) for conditioning the analgesic effect of morphine. Rats were given three pairings of a taste CS with a morphine unconditioned stimulus (US). As expected, there was a decrease in CS intake across repeated pairings, indicating that a conditioned taste aversion was obtained. More important, presentation of the CS alone also increased paw-lick latencies on a hot plate test (either 50°C or 54°C hot plate), suggesting that an analgesic conditioned response (CR) was obtained. The dose of morphine required to produce conditioned analgesia was higher than the dose of morphine required to produce conditioned taste aversion. Using 15 mg/kg morphine, however, both conditioned taste aversion and conditioned analgesia were present when the morphine US was given immediately following CS intake, but not when given 6 h following CS intake. In contrast to morphine, pairing a taste CS with lithium produced a conditioned taste aversion without any conditioned analgesic response. These results indicate that acquisition of an analgesic CR is not the result of stress induced by an aversion to the taste CS.
Similar content being viewed by others
References
Amit Z, Galina ZH (1986) Stress-induced analgesia: adaptive pain suppression. Physiol Rev 66:1091–1120
Cappell H, LeBlanc AE, Endrenyi L (1973) Aversive conditioning by psychoactive drugs: effects of morphine, alcohol and chlordiazepoxide. Psychopharmacology 29:239–246
Eikelboom R, Stewart J (1982) Conditioning of drug-induced physiological responses. Psychol Rev 89:507–528
Fernandes M, Kluwe S, Coper H (1977) The development of tolerance to morphine in the rat. Psychopharmacology 54:197–201
Helmstetter FJ, Fanselow MS (1987) Strain differences in reversal of conditional analgesia by opioid antagonists. Behav Neurosci 101:735–737
Hunskaar S, Berge OG, Hole K (1986) A modified hot-plate test sensitive to mild analgesics. Behav Brain Res 21:101–108
Hunt T, Spivak K, Amit Z (1985) Aversive stimulus properties of morphine: Evaluation using the drug preexposure conditioned taste aversion paradigm. Behav Neural Biol 44:60–73
Jaffe JH, Martin, WR (1990) Opioid analgesics and antagonists. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics. Pergamon, New York, pp 485–521
Kosten TR (1990) Neurobiology of abused drugs: opioids and stimulants. J Nerv Ment Dis 178:217–227
Krank MD, MacQueen GM (1988) Conditioned compensatory responses elicited by environmental signals for cyclophos-phamide-induced suppression of antibody production in mice. Psychobiology 16:229–235
Krank MD, Hinson RE, Siegel S (1981) Conditioned hyperalgesia is elicited by environmental signals of morphine. Behav Neural Biol 32:148–157
Miller JS, Kelly KS, Neisewander JL, McCoy DF, Bardo MT (1990) Conditioning of morphine-induced taste aversion and analgesia. Psychopharmacology 101:472–480
O'Callaghan JP, Holtzman SG (1975) Quantification of the analgesic activity of narcotic antagonists by a modified hot-plate procedure. J Pharmacol Exp Ther 80:300–307
Paletta MS, Wagner AR (1986) Development of context-specific tolerance to morphine: Support for a dual-process interpretation. Behav Neurosci 100:611–623
Poulos CX, Cappell H (1991) Homeostatic theory of drug tolerance: a general model of physiological adaptation. Psychol Rev 98:390–408
Robbins SJ, Ehrman RN (1992) Designing studies of drug conditioning in humans. Psychopharmacology 106:143–153
Schenk S, Hunt T, Klukowski G, Amit Z (1987) Isolation housing decreases the effectiveness of morphine in the conditioned taste aversion paradigm. Psychopharmacology 92:48–51
Smotherman WP (1985) Glucocorticoid and other hormonal substrates of conditioned taste aversion. Ann NY Acad Sci 443:126–144
Terman GW, Shavit Y, Lewis JW, Cannon JT, Liebeskind JC (1984) Intrinsic mechanisms of pain inhibition: activation by stress. Science 226:1270–1277
Tiffany ST, Petrie EC, Baker TB, Dahl JL (1983) Conditioned morphine tolerance in the rat: absence of a compensatory response and cross-tolerance with stress. Behav Neurosci 97:335–353
Watkins LR, Mayer DJ (1982) Organization of endogenous opiate and nonopiate pain control systems. Science 216:1185–1192
Watkins LR, Wiertelak, EP, Grisel JE, Silbert LH, Maier SF (1992) Parallel activation of multiple spinal opiate systems appears to mediate ‘non-opiate’ stress-induced analgesias. Brain Res 594:99–108
Zimet PO, Wynn RL, Ford RD, Rudo FG (1986) Effect of hot plate temperature on the antinociceptive activity of mixed opioid agonist-antagonist compounds. Drug Dev Res 7:277–280
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bardo, M.T., Valone, J.M. Morphine-conditioned analgesia using a taste cue: dissociation of taste aversion and analgesia. Psychopharmacology 114, 269–274 (1994). https://doi.org/10.1007/BF02244848
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244848