title: Prefrontal cortex lesions cause only minor effects on the hyperlocomotion induced by MK-801 and its reversal by clozapine.
abstract: The non-competitive NMDA receptor antagonist MK-801 elicits a behavioural syndrome in rodents characterized by hyperlocomotion and stereotypies, which is antagonized by antipsychotic drugs. NMDA receptor antagonists increase prefrontal cortex (PFC) activity in rodents, as assessed by electrophysiological and neurochemical measures. The increase in glutamate outflow induced by systemic MK-801 administration in the medial PFC (mPFC) is prevented by the local administration of clozapine (Clz). In the present study, we examine whether a PFC lesion alters the behavioural syndrome induced by MK-801 in rats and the Clz-induced antagonism of MK-801 actions. We evaluated the hyperlocomotion, stereotypies and other behavioural changes induced by MK-801 in the open field and the effect of electrolytic lesions of the mPFC, and of cortical transection on the behavioural syndrome induced by MK-801 and its reversal by Clz. MK-801 (0.1-0.2 mg/kg i.p.) reduced rearings but only the higher dose induced hyperlocomotion. At this dose, MK-801 also increased disorganized movements, head weavings, and induced ataxia signs. An electrolytic lesion of the mPFC markedly reduced the number of rearings pre-treatment but caused a very slight attenuation of MK-801-induced hyperlocomotion. Cortical transection did not significantly alter MK-801 effects. Clz administration (1 mg/kg s.c.) significantly attenuated hyperlocomotion, head weavings and ataxia signs induced by MK-801 but did not prevent the decrease in rearings. The effect of Clz was essentially unaffected by electrolytic lesions of the mPFC. These results show that MK-801-induced motor syndrome and its reversal by Clz are mostly independent on PFC integrity.
authors.affiliation: Cell Biology Laboratory, Department of Neurophysiology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. scorza@iibce.edu.uy
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Scorza
authors.forename: María Noel
authors.initials: MN
authors.lastname: Meikle
authors.forename: Ximena López
authors.initials: XL
authors.lastname: Hill
authors.forename: Analía
authors.initials: A
authors.lastname: Richeri
authors.forename: Daniel
authors.initials: D
authors.lastname: Lorenzo
authors.forename: Francesc
authors.initials: F
authors.lastname: Artigas
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003627:Data Interpretation, Statistical; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D017397:Prefrontal Cortex / Q000293:injuries / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D003024:Clozapine