Differential Fos-protein induction in rat forebrain regions after acute and long-term haloperidol and clozapine treatment.
Both acute and long-term effects of haloperidol and clozapine on Fos-like immunoreactive nuclei in several rat forebrain areas were quantified. Rats were treated with saline (1 ml/kg.day, control), haloperidol (1 mg/kg.day) and clozapine (20 mg/kg.day) i.p. for 21 days. Two hours before perfusion fixation a single (acute treatment) or last (long-term treatment) dose of the drug was given. Drug-induced catalepsy and gain in body weight were also measured. A single dose of haloperidol produced large increases in Fos-like immunoreactive nuclei in the striatum, the nucleus accumbens and central amygdala. Following long-term treatment these increases were reduced in all nuclei studied, except the lateral septum. Acute clozapine treatment had slight (if any) effects on the number of Fos-like immunoreactivity-expressing nuclei in the striatum, but the increases in the nucleus accumbens, the lateral septum, the paraventricular and supraoptic nuclei of the hypothalamus and the central amygdala were substantial. Long-term clozapine treatment reduced the acute response significantly in all the areas except the nucleus accumbens. Both haloperidol and clozapine treatment reduced the weight gain of the rats. Haloperidol, but not clozapine, induced catalepsy that remained maximal during the long-term haloperidol treatment. These results indicate that in most brain areas high Fos-protein levels are not necessary to maintain antipsychotic activity or side-effects. The persisting effect of clozapine in the nucleus accumbens may be of significance to the efficacy of this drug in treatment-refractory schizophrenia.
Sebens
J B
JB
Department of Biological Psychiatry, University of Groningen, Netherlands.
Koch
T
T
Ter Horst
G J
GJ
Korf
J
J
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects
D016760:Proto-Oncogene Proteins c-fos; D003024:Clozapine; D006220:Haloperidol