FosB in rat striatum: normal regional distribution and enhanced expression after 6-month haloperidol administration.
Subcortical motor nuclei show differential expression of FosB immediate early gene products and specifically deltaFosB after short (8, 19, or 21 days) chronic exposure to typical and atypical neuroleptics represented by haloperidol and clozapine, respectively. We quantitatively examined whether there are light microscopic regional variations in area density of FosB or the truncated deltaFosB in several motor-related nuclei of adult rats receiving vehicle or long chronic (6 months) administration of either depot haloperidol or clozapine in their drinking water. In control animals the dorsomedial and ventromedial caudate-putamen nucleus (CPN) had a significantly higher density of FosB-immunoreactive cells than the dorsolateral and ventrolateral regions. The nucleus accumbens (NAc) core also serving motor functions had a higher basal expression than the limbic shell region in control animals. The mediolateral gradient in area density of FosB-labeled cells was maintained in animals receiving either haloperidol or clozapine. In animals receiving haloperidol, but not clozapine, however, there was a regionally selective increase in the area density of only FosB-immunoreactive neurons in the dorsolateral and ventrolateral CPN and in both the core and shell of the NAc. Only the animals receiving chronic haloperidol showed vacuous chewing movements, the animal equivalent of tardive dyskinesia in humans. Our results suggest that, whereas the medial striatal neurons are activated under basal conditions, long chronic haloperidol induced FosB expression more exclusively in the lateral CPN and NAc core, implicating these regions specifically in the motor side effects of this drug.
Rodríguez
J J
JJ
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA. jjrodrig@mail.med.cornell.edu
Garcia
D R
DR
Nakabeppu
Y
Y
Pickel
V M
VM
D000818:Animals; D002452:Cell Count; D003024:Clozapine / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D003024:Clozapine; D006220:Haloperidol