Summary
The effects of haloperidol and diazepam were investigated on stereotypies (wall contacts and turn rounds) induced by the non-competitive NMDA antagonist MK-801 in rats. Haloperidol (0.03, 0.10, 0.25 and 0.40mg/kg body weight) caused a dose-dependent antagonism whereas diazepam (3.0 and 5.0 mg/ kg) caused a dose-dependent agonism of the stereotypies induced by 0.30 mg/ kg MK-801 (all drugs given intraperitoneal). Conversely, diazepam (5.0 mg/kg) given alone reduced significantly the number of spontaneous wall contacts and turn rounds. The paradoxial stimulation of MK-801 induced stereotypies by diazepam could be explained by a shift between positive and negative corticostriatothalamic feedback loops envolving GABAergic neurons in favour of the former.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. TINS 13: 266–271
Carlsson M, Carlsson A (1989) The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J Neural Transm 75: 221–226
Clineschmidt BV, Martin GE, Bunting PR, Papp NL (1982) Central sympathomimetic activity of (+)-5-methyl-10-11 -dihydro-5 H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801) a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic properties. Drug Dev Res 2: 135–145
Gill R, Foster AC, Woodruff GN (1987) Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J Neurosci 7: 3343–3349
Hiramatsu M, Cho AK, Nabeshima T (1989) Comparison of the behavioural and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. Eur J Pharmacol 166: 359–366
McAllister KH (1990) Ethological analysis of the effects of MK-801 upon aggressive male mice: similarity to chlordiazepoxide. Pharmacol Biochem Behav 37(1): 101–106
McNamara JO, Russell RD, Rigsbee L, Bonhaus DW (1988) Anticonvulsant and antiepileptogenic actions of MK-801 in the kindling and electroshock models. Neuropharmacology 27: 563–568
Robertson A, MacDonald C (1984) Atypical neuroleptics clozapine and thioridazine enhance amphetamine-induced stereotypy. Pharmacol Biochem Behav 21: 97–101
Serrano A, D'Angio M, Scatton B (1989) NMDA antagonists block restraint-induced increases in extracellular DOPAC in rat nucleus accumbens. Eur J Pharmacol 162: 157–166
Tiedtke PI, Bischoff C, Schmidt WJ (1990) MK-801-induced stereotypy and its antagonism by neuroleptic drugs. J Neural Transm [GenSect] 81: 173–182
Verma A, Kulkarni SK (1992) Modulation of MK-801 response by dopaminergic agents in mice. Psychopharmacology 107: 431–436
Whishaw IQ, Auer RN (1989) Immediate and long-lasting effects on MK-801 on motor activity, spatial navigation in a swimming pool and EGG in the rat. Psychopharmacology 98: 500–507
Zukin SR, Zukin RS (1979) Specific [3H]-phencyclidine binding in rat central nervous system. Proc Natl Acad Sci USA 76: 5372–5376
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Behrens, S., Gattaz, W.F. MK-801 induced stereotypies in rats are decreased by haloperidol and increased by diazepam. J. Neural Transmission 90, 219–224 (1992). https://doi.org/10.1007/BF01250962
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01250962