Expression of Fos protein in the limbic regions of the rat following haloperidol decanoate.
To identify sites of antipsychotic drug action, the effects of acute and chronic haloperidol treatment on Fos protein expression in rat brain regions were examined by immunohistochemical methods. Male Wistar rats were injected with haloperidol decanoate (40 mg/kg, i.m. ) or vehicle. Fourteen days after injection, each rat was given an acute subcutaneous injection of haloperidol (0.25 mg/kg) or vehicle, and was transcardially perfused 2 h after the second injection. A single dose of haloperidol to chronic vehicle-treated rats produced significant increases in Fos-positive neurons in 18 of 21 brain regions examined including the several cortical areas, caudate-putamen, nucleus accumbens, lateral septum, thalamic nuclei, amygdala, hippocampus CA1, mesencephalic dopaminergic nuclei, and periaqueductal grey. The rats treated with acute vehicle after chronic haloperidol showed persistent Fos increases in confined brain regions comprising the lateral and central amygdala, lateral septum, and entorhinal cortex. Additional haloperidol injection to the chronic haloperidol-treated rats induced significant increases in Fos immunoreactivity in more widespread limbic-thalamo-cortical areas, whereas no significant increase was seen in the dorsolateral caudate-putamen. The persisting effects of haloperidol in the limbic and related structures, especially the amygdala, lateral septum, and entorhinal area may be of significance to the efficacy of long-term haloperidol treatment.
Sun
Y J
YJ
Department of Neuropsychiatry, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan.
Suzuki
M
M
Kurachi
T
T
Murata
M
M
Kurachi
M
M
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D008032:Limbic System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C033563:haloperidol decanoate; D006220:Haloperidol