Abstract
The effects of chronic morphine sulfate (5 mg/kg/day for 14 days) on shock discrimination performance of rats were assessed in Experiment I. Significant tolerance developed to the disruptive effects of morphine on performance. A significant increase in discrimination performance was found 48h after the last injection in tests conducted without the injection environment cues present. Ten days after the chronic drug regimen, tests conducted 30 min after exposure to the injection-environment cues revealed no differences between animals previously administered morphine and control animals administered saline. In Experiment II, shock discrimination performance was assessed in a separate group of rats after exposure to a single injection of morphine sulfate (30 mg/kg), which eliminated associative processes, e.g., Pavlovian or instrumental conditioning, as factors in the subsequent behavioral tests for hyperalgesia. Significant changes in discrimination performance (primarily enhanced percent correct to the high shock stimulus) indicative of increased pain sensitivity were obtained in tests conducted 1,2, and 3, but not 9 days after the injection. These experiments indicate that increased pain sensitivity, as opposed to hyperresponsivity operationally measured in traditional analgesia tests (e.g., hot plate, jumpflinch, and tail flick), is a component of morphine withdrawal of a nonassociative origin.
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References
Barnett SA (1963) The rat. Aldine, Chicago
Berkowitz BA, Ceretta KV, Spector S (1974) The influence of physiologic and pharmacologic factors on the disposition of morphine as determined by radioimmunoassay. J Pharmacol Exp Ther 191:527–534
Campbell BA, Masterson FA (1969) Psychophysics of punishment. In: Punishment and aversive behavior. Campbell, BA, Church RM (eds). Appleton-Century-Crofts, New York, pp 1–42
Cappell H, LeBlanc AE (1973) Aversive conditoning by psychoactive drugs: Effects of morphine, alcohol, and chlordiazepoxide. Psychopharmacologia 29:239–246
Cheney DL, Goldstein A (1971) Tolerance to opioid narcotics: Time course and reversibility of physical dependence in mice. Nature 232:477–478
Fennessy MR, Lee JR (1975) The assessment of and the problems involved in the experimental evaluation of narcotic analgesics. In: Ehrenpreis S, Neidle A (eds) Methods in narcotics research. Marcel Dekker, New York, pp 73–97
Gellert VF, Sparber SB (1977)_A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats. j Pharmacol Exp Ther 201:44–54
Graham FK (1973) Habituation and dishabituation of responses innervated by the autonomic nervous system. In: Peeke HVS, Herz MJ (eds) Habituation (vol 1) Behavioral studies. Academic Press, New York, pp 163–218
Green DM, Swets JA (1966) Signal detection theory and psychophysics. Wiley, New York
Grilly DM (1975) Effects of prior experience on differential learning under amphetamine. Psychopharmacologia 43:271–277
Grilly DM (1981) A signal detection analysis of morphine effects on the response bias of rats in a two-shock discrimination task. Life Sciences 28:1883–1888
Grilly DM, Genovese RF (1979) Assessment of shock discrimination in rats with signal detection theory. Perception and Psychophysics 25:466–472
Grilly DM, Genovese RF, Nowak MJ (1980) Effects of morphine, d-amphetamine, and pentobarbital on shock and light discrimination performance in rats. Psychopharmacology 70, 213–217
Hernandez LL, Appel JB (1979) An analysis of some perceptual effects of morphine, chlorpromazine, and LSD. Psychopharmacology 60:125–130
Iwamoto K, Klaassen CD (1977) First-pass effect of morphine in rats. J Pharmacol Exp Ther 200:236–244
Jacquet YJ, Lajtha A (1974) Paradoxical effects after microinjection of morphine in the periaqueductal gray matter in the rat. Science 185:1055–1057
Jaffe J (1980) Drug addiction and drug abuse. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 535–584
Jaffe J, Martin WR (1980) Opioid analgesics and antagonists. In: Gilman AG, Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 494–534
Kayan S, Woods LA, Mitchell CL (1971) Morphine-induced hyperalgesia in rats tested on the hot plate. J Pharmacol Exp Ther 177:509–513
Lal H, Colpaert FC, Laduron P (1975) Narcotic withdrawal-like mouse jumping produced by amphetamine and L-dopa. Eur J Pharmacol 30:113–116
Overton DA (1968) Dissociated learning in drug states (state-dependent learning). In: Efron DE (ed) Psychopharmacology: A review of progress 1957–1967. Proceedings of the sixth annual meeting of neuropsychopharmacology. U.S. Government Printing Office, Washington, D.C., pp 918–930
Rescorla R (1967) Pavlovian conditioning and its proper control procedures. Psychol Rev 74, 71–80
Rollman GB (1977) Signal detection theory measurement of pain. A review and critique. Pain 3:187–211
Sherman JE (1979) The effects of conditioning and novelty on the rat's analgesic and pyretic responses to morphine. Learning and Motivation 10:383–418
Siegel S (1975) Evidence from rats that morphine tolerance is a learned response. J Comp Physiol Psychol 89:498–506
Spector S (1971) Quantiative determination of morphine in serum by radioimmunoassay. J Pharmacol Exp Ther 178:253–258
Stevens DR, Klemm WR (1979) Morphine-naloxone interactions: A role for nonspecific morphine excitatory effects in withdrawal. Science 205:1379–1380
Tilson HA, Rech RH, Stolman S (1973) Hyperalgesia during withdrawal as a means of measuring the degree of dependence in morphine dependent rats. Psychopharmacologia 28:287–300
Weissman A (1973) Jumping in mice elicited-by α-naphthyloxyacetic acid (α-NOAA). J Pharmacol Exp Ther 184:11–17
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Grilly, D.M., Nowak, M.J., Walsh, P.A. et al. Morphine dependence in rats assessed in a shock discrimination task. Psychopharmacology 74, 250–255 (1981). https://doi.org/10.1007/BF00427104
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DOI: https://doi.org/10.1007/BF00427104