Abstract
The place conditioning paradigm was used to assess the ability of the noncompetitive NMDA receptor antagonist, MK-801, to interfere with drug-place associations. MK-801 (0.1 mg/kg, i.p.) attenuated a place preference produced by high, but not low to moderate, doses of amphetamine. Interference with amphetamine place preference learning was not the result of state-dependent retrieval produced by MK-801. Furthermore, MK-801 did not interfere with the expression of a previously established amphetamine place preference. Pretreatment with MK-801 also interfered with lithium-induced conditioned place aversion learning. These results suggest that the attenuation of place preference conditioning produced by MK-801 is the result of its interference with learning rather than with the rewarding properties of drugs.
Article PDF
Similar content being viewed by others
References
Butelman, E. R. (1989). A novel NMDA antagonist, MK-801, impairs performance in a hippocampal-dependent spatial learning task.Pharmacology, Biochemistry & Behavior,34, 13–16.
Carlezon, W. A., Jr.,Mendrek, A., &Wise, R. A. (1995). MK-801 disrupts the expression but not the development of bromocriptine sensitization: A state-dependency interpretation.Synapse,20, 1–9.
Carlezon, W. A., Jr., &Wise, R. A. (1993). Morphine-induced potentiation of brain stimulation reward is enhanced by MK-801.Brain Research,620, 339–342.
Carr, G. D., Fibiger, H. C., &Phillips, A. G. (1989). Conditioned place preference as a measure of drug reward. In J. M. Liebman & S. J. Cooper (Eds.),The neuropharmacological basis of reward (pp. 264–319). Oxford: Oxford University Press, Clarendon Press.
Cervo, L., &Samanin, R. (1995). Effects of dopaminergic and glutamatergic receptor antagonists on the acquisition and expression of cocaine conditioning place preference.Brain Research,673, 242–250.
Clavier, M. C., Nores, W. L., Olsen, R. D., &Vaccarino, A. L. (1996). NMDA antagonist, MK-801, antagonizes the development of morphine-induced conditioned place preference.Society for Neuroscience Abstracts,22, 174.
Collingridge, G. L., &Bliss, T. V. P. (1987). NMDA receptors: Their role in long-term potentiation.Trends in Neurosciences,10, 288–294.
Collingridge, G. L., Kehl, S. J., &McLennan, H. (1983). Excitatory amino acids in synaptic transmission in the Shaffer-collateral-commissural pathway of the rat hippocampus.Journal of Physiology,334, 33–46.
Corbett, D. (1989). Possible abuse potential of the NMDA antagonist MK-801.Behavioural Brain Research,34, 239–246.
Costello, N. L., Carlson, J. N., Glick, S. D., &Bryda, M. (1989). Dose-dependent and baseline-dependent conditioning withd-amphetamine in the place conditioning paradigm.Psychopharmacology,99, 244–247.
Davis, S., Butcher, S. P., &Morris, R. G. M. (1992). The NMDA receptor antagonist D-2-amino-5-phosphopentanoate (D-AP5) impairs spatial learning and LTP in vivo at intracerebral concentrations comparable to those that block LTP in vitro.Journal of Neuroscience,12, 21–24.
Del Pozo, E., Barrios, M., &Baeyens, J. M. (1996). The NMDA receptor antagonist dizocilpine (MK-801) stereoselectively inhibits morphine-induced place preference conditioning in mice.Psychopharmacology,125, 209–213.
Erb, S. M., &Parker, L. A. (1994). Individual differences in novelty-induced activity do not predict strength of amphetamine-induced place conditioning.Pharmacology, Biochemistry & Behavior,48, 581–586.
Falls, W. A., Miserendino, M. J. D., &Davis, M. (1992). Extinction of fear-potentiated startle: Blockade by infusion of an NMDA antagonist into the amygdala.Journal of Neuroscience,12, 854–863.
Gilbert, D., &Cooper, S. J. (1983). Beta-phenylethylamine,d-amphetamine andl-amphetamine-induced place preference conditioning in rats.European Journal of Pharmacology,95, 311–314.
Hargreaves, E. L., &Cain, D. P. (1992). Hyperactivity, hyper-reactivity, and sensorimotor deficits induced by low doses of theN-methyl-Daspartate non-competitive channel blocker MK-801.Behavioural Brain Research,47, 23–33.
Heale, V., &Harley, C. (1990). MK-801 and AP5 impair acquisition but not retention of the Morris milk maze.Pharmacology, Biochemistry & Behavior,36, 145–149.
Herberg, L. J., &Rose, I. C. (1989). The effect of MK-801 and other antagonists of NMDA-type glutamate receptors on brain-stimulation reward.Psychopharmacology,99, 87–90.
Higgins, G. A., Nguyen, P., &Sellers, E. M. (1992). The NMDA antagonist dizocilpine (MK-801) attenuates motivational as well as somatic aspects of naloxone precipitated opioid withdrawal.Life Sciences,50, PL167-PL172.
Hoffman, D. C. (1994). The noncompetitive NMDA antagonist MK-801 fails to block amphetamine-induced place conditioning in rats.Psychopharmacology, Biochemistry & Behavior,47, 907–912.
Hoffman, D. C., &Beninger, R. J. (1988). Selective D1 and D2 dopamine agonists produce opposing effects in place conditioning but not in conditioned taste aversion learning.Pharmacology, Biochemistry & Behavior,31, 1–8.
Jackson, A., Koek, W., &Colpaert, F. C. (1992). NMDA antagonists make learning and recall state-dependent.Behavioural Pharmacology,3, 415–421.
Jeziorski, M., White, F. J., &Wolf, M. E. (1994). MK-801 prevents the development of behavioral sensitization during repeated morphine administration.Synapse,16, 137–147.
Karler, R., Calder, L. D., Chaudhry, I. A., &Turkanis, S. A. (1989). Blockade of “reverse tolerance” to cocaine and amphetamine by MK-801.Life Sciences,45, 599–606.
Keith, J. R., &Rudy, J. W. (1990). Why NMDA-receptor-dependent long-term potentiation may not be a mechanism of learning and memory: Reappraisal of the NMDA-receptor blockade strategy.Psychobiology,18, 251–257.
Kim, H. S., Jang, C. G., &Park, W. K. (1996). Inhibition by MK-801 of morphine-induced conditioned place preference and postsynaptic dopamine receptor supersensitivity in mice.Pharmacology, Biochemistry & Behavior,55, 11–17.
Kim, J. J., DeCola, J. P., Landeira-Fernandez, J., &Fanselow, M. S. (1991).N-methyl-D-aspartate receptor antagonist APV blocks acquisition but not expression of fear conditioning.Behavioral Neuroscience,105, 126–133.
Laviola, G., Dell’Omo, G., Chiarotti, F., &Bignami, G. (1994).d-Amphetamine conditioned place preference in developing mice: Relations with changes in activity and stereotypies.Behavioral Neuroscience,108, 514–524.
Layer, R. T., Kaddis, F. G., Wallace, L. J. (1993). The NMDA receptor antagonist MK-801 elicits conditioned place preference in rats.Pharmacology, Biochemistry & Behavior,44, 245–247.
Lynch, G., &Baudry, M. (1984). The biochemistry of memory: A new and specific hypothesis.Science,224, 1057–1063.
Miserendino, M. J. D., Sananes, C. B., Melia, K. R., &Davis, M. (1990). Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala.Nature,345, 716–718.
Morris, R. G., Anderson, E., Lynch, G. S., &Baudry, M. (1986). Selective impairment of learning and blockade of long-term-potentiation by anN-methyl-D-aspartate receptor antagonist, AP5.Nature,319, 774–776.
Parker, L. A. (1992). Place conditioning in a three- or four-choice apparatus: Role of stimulus novelty in drug-induced conditioning.Behavioral Neuroscience,106, 294–306.
Popik, P., Layer, R. T., &Skolnick, P. (1995). 100 years of ibogaine: Neurochemical and pharmacological actions of a putative antiaddictive drug.Pharmacological Reviews,47, 235–253.
Pudiak, C. M., &Bozarth, M. A. (1993). L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine.Life Sciences,53, 1517–1524.
Ranaldi, R., Bauco, P., &Wise, R. A. (1996). Synergistic effects of cocaine and dizocilpine (MK-801) on brain stimulation reward.Society for Neuroscience Abstracts,22, 935.
Ranaldi, R., French, E., &Roberts, D. C. S. (1996). Systemic pretreatment with MK-801 (dizocilpine) increases breaking points for self-administration of cocaine on a progressive-ratio schedule in rats.Psychopharmacology,128, 83–88.
Reicher, M. A., &Holman, E. W. (1977). Location preference and flavor aversion reinforced by amphetamine in rats.Animal Learning & Behavior,5, 343–346.
Richardson, N. R., Piercey, M. F., Svensson, K., Collins, R. J., Myers, J. E., &Roberts, D. C. (1993). Antagonism of cocaine selfadministration by the preferential dopamine autoreceptor antagonist, (+)-AJ 76.Brain Research,619, 15–21.
Robinson, G. S., Jr.,Crooks, G. B., Jr.,Shinkman, P. G., &Gallagher, M. (1989). Behavioral effects of MK-801 mimic deficits associated with hippocampal damage.Psychobiology,17, 156–164.
Schenk, S., Valadez, A., McNamara, C., House, D. T., Higley, D., Bankson, M. G., Gibbs, S., &Horger, B. A. (1993). Development and expression of sensitization to cocaine’s reinforcing properties: Role of NMDA receptors.Psychopharmacology,111, 332–338.
Shapiro, M. L., &Caramanos, Z. (1990). NMDA antagonist MK-801 impairs acquisition but not performance of spatial working and reference memory.Psychobiology,18, 231–243.
Spyraki, C., Fibiger, H. C., &Phillips, A. G. (1982). Dopaminergic substrates of amphetamine-induced place preference conditioning.Brain Research,253, 185–193.
Staubli, U., Thibault, O., DiLorenzo, M., &Lynch, G. (1989). Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory.Behavioral Neuroscience,103, 54–60.
Steinpreis, R. E., Kramer, M. A., Mix, K. S., &Piwowarczyk, M. C. (1995). The effects of MK-801 on place conditioning.Neuroscience Research,22, 427–430.
Stewart, J., &Druhan, J. P. (1993). Development of both conditioning and sensitization of the behavioral activating effects of amphetamine is blocked by the noncompetitive NMDA receptor antagonist, MK-801.Psychopharmacology,110, 125–132.
Trujillo, K.A., &Akil, H. (1991). Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801.Science,251, 85–87.
Tzschentke, T., &Schmidt, W. J. (1995).N-methyl-D-aspartic acidreceptor antagonists block morphine-induced conditioned place preference in rats.Neuroscience Letters,193, 37–40.
van der Kooy, D. (1987). Place conditioning: A simple and effective method for assessing the motivational properties of drugs. In M. A. Bozarth (Ed.),Methods of assessing the reinforcing properties of abused drugs (pp. 229–240). New York: Springer-Verlag.
Wall, A.-M., Hinson, R. E., Schmidt, E., Johnston, C., &Streather, A. (1990). Place conditioning withd-amphetamine: The effect of CS-UCS interval and evidence of a place avoidance.Animal Learning & Behavior,18, 393–400.
Welzl, H., Alessandri, B., &Bättig, K. (1990). The formation of a new gustatory memory trace in rats is prevented by the noncompetitive NMDA antagonist ketamine.Psychobiology,18, 43–47.
Author information
Authors and Affiliations
Corresponding author
Additional information
This research was supported by a research grant from the Natural Sciences and Engineering Research Council of Canada to Linda Parker (NSERC-OGP 92057). We thank Marion Corrick for maintaining the health of the animals during these experiments. We also thank Shepard Siegel for valuable discussions of the data throughout the conduct of these experiments. The amphetamine was generously supplied by NIDA. Portions of this manuscript were presented at the Conference on Comparative Cognition in Melbourne, Florida, 1997.
Rights and permissions
About this article
Cite this article
Toth, J.F., Parker, L.A. MK-801 interferes with the acquisition of amphetamine- and lithium-induced place conditioning. Animal Learning & Behavior 27, 481–489 (1999). https://doi.org/10.3758/BF03209983
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.3758/BF03209983