Po. Tremblay et al., MODIFICATION OF HALOPERIDOL-INDUCED PATTERN OF C-FOS EXPRESSION BY SEROTONIN AGONISTS, European journal of neuroscience, 10(11), 1998, pp. 3546-3555
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.