DIFFERENTIAL EXPRESSION OF C-FOS MESSENGER-RNA IN RAT PREFRONTAL CORTEX, STRIATUM, N ACCUMBENS AND LATERAL SEPTUM AFTER TYPICAL AND ATYPICAL ANTIPSYCHOTICS - AN IN-SITU HYBRIDIZATION STUDY

The regional difference in the expression of c-fos mRNA induced by typ ical and atypical antipsychotics was determined in prefrontal cortex, striatum, N. accumbens and lateral septum in rats by in situ hybridiza tion. Two typical antipsychotics, haloperidol (2 mg/kg) and fluphenazi ne (2 mg/kg), and three atypical antipsychotics, (-)sulpiride (100 mg/ kg), clozapine (20 mg/kg) and OPC-14597 (40 mg/kg), were used. Brains were fixed with 4% paraformaldehyde 45 min after drug administration ( i.p.) Brain sections of 30 mu m-thickness were made in a cryostat and hybridized with S-35-labelled for c-fos oligonucleotide probe. These s ections were apposed to X-ray films and the autoradiograms were semi-q uantitatively analysed by computer-assisted densitometry. All antipsyc hotics used increased c-fos mRNA expression in N. accumbens shell, a r egion of the forebrain associated with limbic systems. On the other ha nd, two typical antipsychotics (haloperidol and fluphenazine) that cau se a high incidence of acute motor side effects increased the expressi on of c-fos mRNA in the dorsolateral striatum, ail extrapyramidal regi on primarily involved in motor control. Only clozapine induced c-fos m RNA in the medial prefrontal cortex and lateral septum. These results strongly suggest that the shell region of N. accumbens may be a common site of therapeutic action of antipsychotics. Copyright (C) 1996 Else vier Science Ltd.