Differential effects of chronic treatment with haloperidol and clozapine on the level of preprosomatostatin mRNA in the striatum, nucleus accumbens, and frontal cortex of the rat.
1. The goal of this work was to determine the effects of typical and atypical neuroleptics on the level of preprosomatostatin messenger RNA (mRNA) in regions of the rat brain innervated by dopaminergic neurons. 2. Quantitative in situ hybridization histochemistry was used to measure the levels of mRNA encoding preprosomatostatin in neurons of the striatum, the nucleus accumbens, and the medial and lateral agranular areas of the frontal cortex in adult rats treated with either haloperidol or clozapine. 3. In untreated animals, the density of neurons containing preprosomatostatin mRNA was higher in the nucleus accumbens than in the striatum and frontal cortex. The intensity of labeling per neuron, however, was higher in the striatum than in the two other areas examined, suggesting that the expression of preprosomatostatin mRNA is differentially regulated in these brain regions. Chronic administration of haloperidol (1 mg/kg for 28 days) induced a significant decrease in the labeling for preprosomatostatin mRNA in neurons of the nucleus accumbens, frontal cortex, and medial but not lateral striatum. Treatment with clozapine (20 mg/kg for 28 days) increased the levels of preprosomatostatin mRNA in the nucleus accumbens but not in the striatum or the frontal cortex. 4. These results support a role for dopamine in the regulation of central somatostatinergic neurons. The differences in the effects of haloperidol, a neuroleptic which induces extrapyramidal side effects, and clozapine, which does not, suggest that somatostatinergic neurons may play an important role in the regulation of motor behavior.
Salin
P
P
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Mercugliano
M
M
Chesselet
M F
MF
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003984:Dibenzazepines / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009693:Nucleic Acid Hybridization; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000235:genetics* / Q000378:metabolism
D003984:Dibenzazepines; D011498:Protein Precursors; D012333:RNA, Messenger; D013004:Somatostatin; D003024:Clozapine; D006220:Haloperidol