MODIFICATION OF HALOPERIDOL-INDUCED PATTERN OF C-FOS EXPRESSION BY SEROTONIN AGONISTS

Acute challenge with clozapine and haloperidol produce different anato mical patterns of c-fos expression in the forebrain. The pharmacologic al profile of atypical antipsychotics suggests that serotonin might co ntribute to the unique therapeutic benefits of these drugs. In order t o test this possibility, we examined the abilities of 5-HT1A and 5-HT2 A/2C agonists to modify the pattern of c-fos expression induced by hal operidol and clozapine. Various groups of rats were pretreated with ei ther saline, DOI, 8-OH-DPAT, and 8-OH-DPAT + DOI 30 min prior to halop eridol or clozapine administration. Rats were killed 90 min after anti psychotic administration. In saline-pretreated rats, haloperidol produ ced intense Fos-LI in all four striatal quadrants while the effect of clozapine was restricted to the medial part of the striatum. Prior adm inistration of 8-OH-DPAT significantly reduced haloperidol-induced Fos -LI in all four striatal quadrants while DOI and 8-OHDPAT + DOI signif icantly reduced Fos-LI only in dorso- and ventrolateral quadrants. In the nucleus accumbens, haloperidol induced intense Fos-LI in the core and the shell regions whereas clozapine induced c-fos expression only in the shell. Pretreatment with 8-OHDPAT in haloperidol treated rats r educed Fos-LI in the core region yielding to a c-fos pattern similar t o that induced by clozapine. In the prefrontal cortex of saline-pretre ated rats, haloperidol produced a moderate c-fos expression compared w ith the intense expression produced by clozapine. Pretreatment with se rotonin agonists before haloperidol brought the number of FOS-positive neurons to the same level as in clozapine treated fats. These results show the ability of 5-HT agonists to transform the typical pattern of c-fos expression induced by haloperidol into a pattern resembling tha t of clozapine.