Abstract
The D2 or D1 dopamine receptor blockers (−)-sulpiride or SCH 23390 antagonized, in a dose dependent manner, the hypermotility induced by the N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (0.25 mg/kg IP). MK-801 induced hyperactivity was not detected when rats were observed on days 7, 14 or 21 of 21 daily injections of MK-801. This lack of hyperactivity was also noted 5 days after the last administration of the repeated treatment with MK-801. The hypermotility induced by the D2 dopamine receptor agonist LY 171555 (0.3 mg/kg IP) was reduced 5 days following repeated treatment (21 days) with MK-801, while no change in the behavioral responses to the selective D1 agonist, SKF 38393, or the mixed D1/D2 agent apomorphine was detected. The results, although suggesting the involvement of dopaminergic pathways in the behavioral effect of MK-801, are conflicting with regard to the underlying mechanisms and to the adaptive changes of dopaminergic system following repeated NMDA receptor blockade.
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References
Carlsson M, Carlsson A (1989a) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm 75:221–226
Carlsson M, Carlsson A (1989b) Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. J Neural Transm 77:65–71
Carlsson M, Svensson A (1990) Interfering with glutamatergic neurotransmission by means of NMDA administration discloses the locomotor stimulatory potential of other transmitter systems. Pharmacol Biochem Behav 36:45–50
Clineschmidt BV, Martin GE, Bunting PR (1982a) Anticonvulsant activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclophepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic and apparent anxiolitic properties. Drug Dev Res 2:123–134
Clineschmidt BV, Martin GE, Bunting PR, Papp NL (1982b) Central sympathomimetic activity of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclo- phepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic and apparent anxiolitic properties. Drug Dev Res 2:135–145
Clineschmidt BV, Williams M, Witolslawski JJ, Bunting PR, Risley EA, Totaro JA (1982c) Restoration of shock-suppressed behavior by treatment with (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclo- phepten-5,10-imine (MK-801), a substance with potent anticonvulsant, central sympathomimetic and apparent anxiolitic properties. Drug Dev Res 2:147–163
Dall'Olio R, Roncada P, Vaccheri A, Gandolfi O, Montanaro N (1989) Synergistic blockade of some dopamine-mediated behaviors by (−)-sulpiride and SCH 23390 in the rat. Psychopharmacology 98:342–346
Dimpfel W, Spuler M (1990) Dizocilpine (MK-801), ketamine and phencyclidine: low doses affect brain field potentials in the freely moving rat in the same way as activation of dopaminergic transmission. Psychopharmacology 101:317–323
Gandolfi O, Dall'Olio R, Vaccheri A, Roncada P, Montanaro N (1988) Responses to selective D1 and D2 agonists after repeated treatment with selective D1 and D2 antagonists. Pharmacol Biochem Behav 30:463–469
Gill R, Foster AC, Woodruff GN (1987) Systemic administration of MK-801 protects against ischaemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7:3343–3349
Hiramatsu M, Cho AK, Nabeshima T (1989) Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. Eur J Pharmacol 166:359–366
Iwamoto ET (1986) Comparison of the pharmacologic effects of N-allylnormetazocine and phencyclidine: Sensitization, cross-sensitization, and opioid antagonistic activity. Psychopharmacology 89:221–229
Klawans HL, Margolin DI (1975) Amphetamine-induced dopaminergic hypersensitivity in guinea-pigs. Arch Gen Psychiatry 32:725–732
Liljequist S, Ossowska K, Grabowska-Anden M, Anden NE (1991) Effect of the NMDA receptor antagonist, MK-801, on locomotor activity and on the metabolism of dopamine in various brain areas of mice. Eur J Pharmacol 195:55–61
Oles RJ, Singh L, Tricklebank MD (1990) Differential effects on the behavioural and anticonvulsant properties of MK-801 following repeated administration in the mouse. Br J Pharmacol 99:286P
Rao TS, Kim HS, Lehmann J, Martin LL, Wood PL (1990) Selective activation of dopaminergic pathways in the mesocortex by compounds that act at the phencyclidine (PCP) binding site: tentative evidence for PCP recognition sites not coupled to N-methyl-d-aspartate (NMDA) receptors. Neuropharmacology 29:225–230
Robinson TE, Becker JB (1986) Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res Rev 11:157–198
Segal DS, Mandell AJ (1974) Long-term administration of amphetamine: progressive augmentation of motor activity and stereotypy. Pharmacol Biochem Behav 2:249–255
Wong EHF, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL (1986) The anticonvulsant MK-801 is a potent N-methyl-d-aspartate antagonist. Proc Natl Acad Sci USA 83:7104–7108
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Dall'Olio, R., Gandolfi, O. & Montanaro, N. Effect of chronic treatment with dizocilpine (MK-801) on the behavioral response to dopamine receptor agonists in the rat. Psychopharmacology 107, 591–594 (1992). https://doi.org/10.1007/BF02245275
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DOI: https://doi.org/10.1007/BF02245275