NMDA receptor blockade attenuates the haloperidol induction of Fos protein in the dorsal but not the ventral striatum.
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.
de Souza
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IE
Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland. desouzai@tcd.ie
Meredith
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GE
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*
D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006220:Haloperidol