c-Fos and FosB/ΔFosB colocalizations in selected forebrain structures after olanzapine, amisulpride, aripiprazole, and quetiapine single administration in rats preconditioned by two different mild stressors sequences

The present findings indicate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell, in both HDL and CMS preconditioned rats, whereas the parallel occurrence of free c-Fos as well as c-Fos colocalized with ΔFosB might speak out for a possible involvement of the c-Fos activated by antipsychotics applied in dual, i.e. short- and long-lasting, functions.

The rats were divided into 10 groups and exposed to two types of stressors. Half of them was exposed to a sequence of homogeneous stressor - handling (HDL) and the other half to a heterogeneous stressor (CMS) daily for 20 days. CMS consisted of five types of stressors: crowding, air-puff, wet bedding, predator stress, and forced swimming applied in an unexpected order. On the 21st day of the experiment, the rats were free of the stress exposure and on the 22nd day, both groups of animals receive a single intraperitoneal injection of vehicle (4% DMSO in saline, 0.1 ml/100 g) or OLA (5 mg/kg), AMI (20 mg/kg), ARI (10 mg/kg), and QUE (15 mg/kg). 90 min after the drugs administration the animals were transcardially perfused, brains removed, cut into 30 µm thick coronal sections, and double stained: first with ΔFosB antibody linked with Alexa488 fluorescent dye and second with c-Fos antibody linked to Alexa596 one. Quantitative evaluation of ΔFosB and c-Fos colocalizations was performed on fluorescence photomicrographs transformed into a final picture containing only yellow, green, and red colored circles.

Olanzapine (OLA), amisulpride (AMI), aripiprazole (ARI), and quetiapine (QUE) belong to antipsychotics, which administration represents still most reliable way for the treatment of schizophrenic and bipolar disorders. The intention of the present study was to explore whether the acute administration of a particular antipsychotic, indicated by the presence of c-Fos, will: a) stimulate neurons already activated by a long lasting homogeneous or heterogeneous stress preconditioning, indicated by the FosB/ΔFosB (ΔFosB) expression, or b) have a stimulatory effect only on a not activated, so called silent neurons. The pattern of ΔFosB and c-Fos spatial relationship was investigated in three forebrain structures, including the septal ventrolateral nucleus (seVL), the striatal dorsolateral area (stDL), and the shell of the nucleus accumbens (shell).

The data of this investigation demonstrate that ΔFosB and c-Fos colocalizations occurred in each of the three areas investigated, i.e. seVL, stDL, and shell ones, in both HDL as well as CMS preconditioned rats. The levels of ΔFosB and c-Fos colocalizations varied in the individual forebrain areas studied. From the total 22 areas measured, level of c-Fos colocalization prevailed over ΔFosB in 18 ones. However, neither c-Fos nor ΔFosB reached 100% level of colocalization in any of the forebrain areas investigated.