Abstract
The present experiment was designed to examine whether the acute sensitization to naltrexone that is induced by a single dose of morphine could be blocked by pretreatment with naloxone. Food-deprived male Sprague-Dawley rats were trained to respond for food on a multiple-trial fixed interval 3-min schedule. Reinforcement was contingent upon a response within a 10-s limited hold period following a fixed interval of 3 min. A trial consisted of three fixed intervals separated by a 10-min timeout period during which responses were not reinforced. The rate decreasing effects of the opioid antagonist naltrexone were determined by cumulative dosing. Pretreatment with morphine (3.0 mg/kg, SC) resulted in a 70-fold increase in sensitivity to the response rate decreasing effect of naltrexone compared with saline pretreatment. The increased sensitivity was dose-dependently blocked by naloxone administration 10 min before morphine. The blockade by naloxone was overcome by increasing the pretreatment dose of morphine to 10 mg/kg. The results provide further evidence that acute agonist-induced sensitization to the rate-reducing effects of naltrexone is mediated by opioid receptors.
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References
Adams JU, Holtzman SG (1990) Pharmacological characterization of the sensitization of the rate-decreasing effects of naltrexone induced by acute opioid pretreatment in rats. J Pharmacol Exp Ther 253:483–489
Balster RL (1985) Behavioral studies of tolerance and dependence. In: Seiden LS, Balster RL (eds) Behavioral pharmacology: the current status. Liss, New York, pp 403–418
Eisenberg RM (1982) Further studies on the acute dependence produced by morphine in opiate naive rats. Life Sci 31:1531–1540
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
Goldberg SR, Morse WH, Goldberg DM (1981) Acute and chronic effects of naltrexone and naloxone on schedule-controlled behavior of squirrel monkeys and pigeons. J Pharmacol Exp Ther 216:500–509
Herling S (1981) Effects of naltrexone dose and history of naltrexone exposure on food and codeine-maintained responding in rhesus monkeys. J Pharmacol Exp Ther 217:105–113
Holtzman SG, Villarreal JE (1973) Operant behavior in the morphine-dependent rhesus monkey. J Pharmacol Exp Ther 184:528–541
Kosersky DS, Harris RA, Harris LS (1974) Naloxone-precipitated jumping activity in mice following the acute administration of morphine. Eur J Pharmacol 26:122–124
Meyer DR, Sparber SB (1977) Evidence of possible opiate dependence during the behavioral depressant action of a single dose of morphine. Life Sci 21:1087–1094
Nakaki T, Saito M, Nakadat T, Tonkanaga Y, Kato R (1981) Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat. Psychopharmacology 73:215–218
Schindler CW, Wu XZ, Su T-P, Goldberg SR, Katz JL (1990) Enhanced sensitivity to behavioral effects of naltrexone in rats. J Pharmacol Exp Ther 252:8–14
Schindler CW, Goldberg SR, Katz JL (1993) Pharmacological specificity of enhanced sensitivity to naltrexone in rats. Psychopharmacology 110:60–68
Spealman RD, Kelleher RT, Morse WH, Goldberg SR (1981) Supersensitivity to the behavioral effect of opiate antagonists. Psychopharmacol Bull 17:54–56
Tulunay FC, Takemori AE (1974) The increased efficiency of narcotic antagonists induced by various narcotic analgesics. J Pharmacol Exp Ther 190:395–400
White-Gbadebo D, Holtzman SG (1993) Acute sensitization to opioid antagonists. Pharmacol Biochem Behav (in press)
Wong CL, Bentley GA (1978) Increased antagonist potency of naloxone caused by morphine pretreatment in mice. Eur J Pharmacol 47:415–422
Yano I, Takemori AE (1977) Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. Res Commun Chem Pathol Pharmacol 16[4]: 721–734
Young AM (1986) Effects of acute morphine pretreatment on the rate-decreasing and antagonist activity of naloxone. Psychopharmacology 88:201–208
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White-Gbadebo, D., Holtzman, S. Naloxone pretreatment blocks acute morphine-induced sensitization to naltrexone. Psychopharmacology 114, 225–228 (1994). https://doi.org/10.1007/BF02244840
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DOI: https://doi.org/10.1007/BF02244840