FosB in rat striatum: Normal regional distribution and enhanced expressionafter 6-month haloperidol administration

Subcortical motor nuclei show differential expression of FosB immediate ear ly gene products and specifically Delta FosB after short (8, 19, or 21 days ) chronic exposure to typical and atypical neuroleptics represented by halo peridol and clozapine, respectively. We quantitatively examined whether the re are light microscopic regional variations in area density of FosB or the truncated Delta FosB in several motor-related nuclei of adult rats receivi ng vehicle or long chronic (6 months) administration of either depot halope ridol or clozapine in their drinking water. In control animals the dorsomed ial and ventromedial caudate-putamen nucleus (CPN) had a significantly high er density of FosB-immunoreactive cells than the dorsolateral and ventrolat eral regions. The nucleus accumbens (NAc) core also serving motor functions had a higher basal expression than the limbic shell region in control anim als. The mediolateral gradient in area density of FosB-labeled cells was ma intained in animals receiving either haloperidol or clozapine. In animals r eceiving haloperidol, but not clozapine, however, there was a regionally se lective increase in the area density of only FosB-immunoreactive neurons in the dorsolateral and ventrolateral CPN and in both the core and shell of t he NAc. Only the animals receiving chronic haloperidol showed vacuous chewi ng movements, the animal equivalent of tardive dyskinesia in humans. Our re sults suggest that, whereas the medial striatal neurons are activated under basal conditions, long chronic haloperidol induced FosB expression more ex clusively in the lateral CPN and NAc core, implicating these regions specif ically in the motor side effects of this drug. (C) 2001 Wiley-Liss, Inc.