EFFECT OF CHRONIC ANTIPSYCHOTIC DRUG-TREATMENT ON PREPROSOMATOSTATIN AND PREPROTACHYKININ-A MESSENGER-RNA LEVELS IN THE MEDIAL PREFRONTAL CORTEX, THE NUCLEUS-ACCUMBENS AND THE CAUDATE-PUTAMEN OF THE RAT

In situ hybridization histochemistry was used to study the expression of preprosomatostatin (PPSOM) and preprotachykinin A (PPT-A) mRNA in t he medial prefrontal cortex (mPFC), the nucleus accumbens (NAC) and th e caudate putamen (CP) of the rat after chronic (21 days) treatment wi th the classical antipsychotic drug haloperidol (1 mg/kg i.p.), the at ypical antipsychotic drugs clozapine (15 mg/kg i.p.) and amperozide (5 mg/kg i.p.), and the selective dopamine (DA)-D-2/D-3 receptor antagon ist raclopride (2 mg/kg i.p.). Whereas amperozide markedly elevated th e numerical density of PPSOM mRNA expressing neurons in the mPFC (52%) , the other drugs did not significantly affect PPSOM mRNA levels in an y of the brain regions studied. Amperozide also altered PPT-A mRNA exp ression in the mPFC, i.e. a decrease (22%) was found. Of the other dru gs tested only haloperidol significantly decreased PPT-A mRNA levels i n the NAC shell (14%), in the dorso-lateral CP (19%) and in the medial CP (15%). In view of the differences between amperozide and the other drugs studied, as regards both pre-clinical and clinical characterist ics, we suggest that the specific effects of amperozide on PPSOM and P PT-A mRNA in the mPFC may be related to its 5-HT releasing action in t he frontal cortex, an effect possibly caused by its alpha(2)-adrenocep tor blocking activity. This effect, in turn, may be related to an anti depressant-like action that this compound exhibits in animal studies. The decrease in PPT-A mRNA levels seen after the haloperidol treatment is probably due to its potent DA-D-2 receptor antagonism and may be r elated to side-effects, rather than therapeutic effects of this drug.