Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary

Abstract

We examined the effect of chronic administration (14 days) of haloperidol (2 mg/kg/day) or sulpiride (100 mg/kg/day), on the mRNA levels of various genes in the rat striatum and pituitary by quantitative in situ and Northern blot hybridizations. In the pituitary, haloperidol and sulpiride induced similar increases of mRNAs of pro-opiomelanocortin (POMC) (+65% and +73%), prolactin (PRL) (+821% and +840%) and growth hormone (GH) (+32% and +47%), but sulpiride induced a greater increase of D2R mRNA (+125%) than haloperidol (+92%). In the striatum, sulpiride and haloperidol had different effects: sulpiride induced a higher increase than haloperidol of both preproenkephalin A (PPA) mRNA (+67% versus +47%) and D 2 dopamine receptor (D 2R) mRNAs (+72% versus +40%). Moreover, haloperidol and sulpiride had opposite effects on substance P (SP) mRNA. Haloperidol decreased the amount of SP mRNA by 20% while sulpiride increased it by 20%. The D 1 dopamine receptor (D 1R) mRNA level was not significantly modified after either treatment. Our results demonstrate that the effect of a chronic haloperidol treatment on striatal dopamine receptors and neuropeptide mRNA levels is different to that of sulpiride, whereas it is similar on pituitary hormones mRNA levels.