title: NMDA receptor blockade attenuates the haloperidol induction of Fos protein in the dorsal but not the ventral striatum.
abstract: Neuroleptic blockade of dopamine receptors is known to produce an increase in the expression of Fos. This increase may be related to elevations in glutamate transmission which in turn activates N-methyl-D-aspartate (NMDA) receptors. In the present study, we examine the role of these receptors in the haloperidol-induced augmentation of Fos in the caudate-putamen and nucleus accumbens of Wistar rats. Animals were divided into four groups for each experiment and each was injected either with saline; a noncompetitive NMDA antagonist, dizocilpine maleate (MK801, 5 mg/kg); haloperidol (0.5 mg/kg); or MK801 followed by an injection of haloperidol. Fos-immunoreactive cells appear in large numbers in all parts of the striatum 3 h after the administration of haloperidol. Pretreatment with MK801 attenuates the haloperidol-induced increase in Fos in the caudate-putamen. However, antagonism of the NMDA receptor does not significantly reduce the density of Fos-immunoreactive cells in any territory of nucleus accumbens, i.e., shell, core, or rostral pole. These data suggest that haloperidol acts in an NMDA-dependent manner in the caudate-putamen, but independently in parts of nucleus accumbens traditionally considered to be targets of antipsychotic drugs.
authors.affiliation: Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland. desouzai@tcd.ie
authors.forename: I E
authors.initials: IE
authors.lastname: de Souza
authors.forename: G E
authors.initials: GE
authors.lastname: Meredith
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006220:Haloperidol