Abstract
The effect of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) on conditioned place preference induced by morphine was studied in mice. As expected, morphine (1–8 mg/kg, IP) elicited a significant preference for the drug-paired compartment. Pretreatment of mice with (+)-dizocilpine (0.1 and 0.2 mg/kg, IP), the more active dizocilpine enantiomer, dose-dependently reversed the conditioned place preference produced by morphine (4 mg/kg, IP), whereas (−)-dizocilpine (0.2 mg/kg, IP) did not modify morphine-induced effects. In contrast, both enantiomers of dizocilpine (at a dose of 0.2 mg/kg, IP) elicited a conditioned place preference. These data suggest that (1) NMDA receptors play a role in morphine-induced place preference, and (2) dizocilpine-reinforcing properties in the place preference paradigm do not seem to be dependent on NMDA receptor blockade.
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References
Bardo MT, Miller JS, Neisewander JL (1984) Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR. Pharmacol Biochem Behav 21:545–549
Bardo MT, Neisewander JL, Miller JS (1986) Repeated testing attenuates conditioned place preference with cocaine. Psychopharmacology 89:239–243
Barr GA, Paredes W, Bridger WH (1985) Place conditioning with morphine and phencyclidine: dose dependent effects. Life Sci 36:363–368
Beardsley PM, Hayes BA, Balster RL (1990) The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys. J Pharmacol Exp Ther 252:953–959
Ben-Eliyahu S, Marek P, Vaccarino AL, Mogil JS, Sternberg WF, Liebeskind JC (1992) The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat. Brain Res 575:304–308
Bespalov A, Dumpis M, Piotrovsky L, Zvartau E (1994) Excitatory amino acid receptor antagonist kynurenic acid attenuates rewarding potential of morphine. Eur J Pharmacol 264:233–239
Carr GD, White NM (1983) Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Life Sci 33:2551–2557
Chen L, Huang LY (1991) Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid. Neuron 7:319–326
Fundytus ME, Coderre TJ (1994) Effect of activity at metabotropic, as well as ionotropic (NMDA), glutamate receptors on morphine dependence. Br J Pharmacol 113:1215–1220
Galbicka G, Kautz MA, Jagers T (1994) Behavioral effect of enantiomers of dizocilpine under two “counting” procedures in rats. Pharmacol Biochem Behav 49:943–948
Garcia MM, Harlan RE (1993) Chronic morphine increases calbindin D28k in rat striatum: possible NMDA receptor involvement. Neuroreport 5:65–68
Gudehithlu KM, Reddy PL, Barghava HN (1994) Effect of morphine tolerance and abstinence on the binding of [3H]MK-801 to brain regions and spinal cord of the rat. Brain Res 639:269–274
Heale V, Harley C (1990) MK-801 and AP5 impair acquisition, but not retention, of the Morris milk maze. Pharmacol Biochem Behav 36:145–149
Herberg LJ, Rose IC (1989) The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward. Psychopharmacology 99:87–90
Hoffman DC (1994) The noncompetitive NMDA antagonist MK-801 fails to block amphetamine-induced place conditioning in rats. Pharmacol Biochem Behav 47:907–912
Jeziorski M, White FJ, Wolf ME (1994) MK-801 prevents the development of behavioural sensitization during repeated morphine administration. Synapse 16:137–147
Layer RT, Kaddis FG, Wallace LJ (1993) The NMDA receptor antagonist MK-801 elicits conditioned place preference in rats. Pharmacol Biochem Behav 44:245–247
Lodge D, Johnson KM (1990) Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol Sci 11:81–86
Löscher W, Annies R, Hönack D (1993) Comparison of competitive and uncompetitive NMDA receptor antagonists with regard to monoaminergic neuronal activity and behavioural effects in rats. Eur J Pharmacol 242:263–274
Lutfy K, Hurlburt DE, Weber E (1993) Blockade of morphine-induced analgesia and tolerance in mice by MK-801. Brain Res 616:83–88
Marek P, Ben-Eliyahu S, Gold M, Liebeskind JC (1991a) Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat. Brain Res 547:77–81
Marek P, Ben-Eliyahu S, Vaccarino AL, Liebeskind JC (1991b) Delayed application of MK-801 attenuates development of morphine tolerance in rats. Brain Res 558:163–165
Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247
Price GW, Ahier RG, Middlemiss DN, Singh L, Tricklebank MD, Wong EH (1988) In vivo labelling of the NMDA receptor channel complex by [3H]MK-801. Eur J Pharmacol 158:279–282
Ransom RW, Stec NL (1988) Inhibition ofN-methyl-d-aspartate evoked sodium flux by MK-801. Brain Res 444:25–32
Self DW, Stein L (1992) Receptor subtypes in opioid and stimulant reward. Pharmacol Toxicol 70:87–94
Spyraki C (1988) Drug reward studies by the use of place conditioning in rats. In: Lader M (ed) The psychopharmacology of addiction. Oxford University Press, Oxford New York Tokyo, pp 97–114
Stolerman I (1992) Drugs of abuse: behavioural principles, methods and terms. Trends Pharmacol Sci 13:170–176
Stone TW (1993) Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 45:309–379
Suzuki T, Funada M, Narita M, Misawa M, Nagase H (1991) Pertussis toxin abolishesμ- andδ-opioid agonist-induced place preference. Eur J Pharmacol 205:85–88
Suzuki T, Funada M, Narita M, Misawa M, Nagase H (1993) Morphine-induced place preference in the CXBK mouse: characteristics ofμ opioid receptor subtypes. Brain Res 602:45–52
Tang AH, Ho PM (1988) Both competitive and non-competitive antagonists ofN-methyl-d-aspartic acid disrupt brightness discrimination in rats. Eur J Pharmacol 151:143–146
Trujillo KA, Akil H (1991) Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 251:85–87
Trujillo KA, Akil H (1994) Inhibition of morphine tolerance by non-competitiveN-methyl-d-aspartate receptor antagonists. Brain Res 633:178–188
White NM, Carr GD (1985) The conditioned place preference is affected by two independent reinforcement processes. Pharmacol Biochem Behav 23:37–42
Wolf ME, Jeziorski M (1993) Coadministration of MK-801 with amphetamine, cocaine or morphine prevents rather than transiently masks the development of behavioral sensitization. Brain Res 613:291–294
Xie CW, Lewis DV (1991) Opioid mediated facilitation of long-term potentiation at the lateral perforant path-dentate granule cell synapse. J Pharmacol Exp Ther 256:289–296
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Del Pozo, E., Barrios, M. & Baeyens, J.M. The NMDA receptor antagonist dizocilpine (MK-801) stereoselectively inhibits morphine-induced place preference conditioning in mice. Psychopharmacology 125, 209–213 (1996). https://doi.org/10.1007/BF02247330
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DOI: https://doi.org/10.1007/BF02247330