Clozapine impact on FosB/ΔFosB expression in stress preconditioned rats: response to a novel stressor

Abstract

Objective. Prolonged treatment with neuroleptics has been shown to induce FosB/ΔFosB expression in several brain regions including the medial prefrontal cortex, dorsomedial and dorsolateral striatum, ventrolateral and dorsolateral septum, nucleus accumbens shell and core, and the hypothalamic paraventricular nucleus (PVN). Some of these regions are known to be also stress responsive. This study was designed to determine whether repeated clozapine (CLZ) administration for 7 consecutive days to Wistar rats may modify FosB/ΔFosB expression in the above-mentioned brain areas induced by acute stress or novel stressor that followed 13-day chronic mild stress preconditioning.Methods. Following experimental groups were used: unstressed animals treated with vehicle/ CLZ for 7 days; 7-day vehicle/CLZ-treated animals on the last day exposed to acute stress – forced swimming (FSW); and animals preconditioned with stress for 13 days treated from the 8th day with vehicle/CLZ and on the 14th day exposed to novel stress – FSW.Results. In the unstressed animals CLZ markedly increased FosB/ΔFosB immunoreactivity in the ventrolateral septum and PVN. FSW elevated FosB/ΔFosB expression in the medial prefrontal cortex, striatum, and septum. CLZ markedly potentiated the effect of the FSW on FosB/ΔFosB expression in the PVN, but suppressed it in the dorsomedial striatum. Novel stress with stress preconditioning increased FosB/ΔFosB immunoreactivity in the prefrontal cortex, striatum, ventrolateral septum, and the PVN. In the nucleus accumbens the effect of the novel stressor was potentiated by CLZ.Conclusion. Our data indicate that CLZ may modulate the acute as well as novel stress effects on FosB/ΔFosB expression but its effect differs within the individual brain regions.

Preventive Roles of Rice-koji Extracts and Ergothioneine on Anxiety- and Pain-like Responses under Psychophysical Stress Conditions in Male Mice

“…These proteins are transcriptional factors and exert their effects by enhancing or repressing the expression of other genes and are involved in the development and maintenance of anxiety and nociception. In general, acute stress increases c-Fos and FosB expressions in the PVN [ 58 , 59 ], whereas the effect of chronic stress on c-Fos and FosB expressions seems to be bidirectional [ 60 , 61 , 62 ]. Evidence demonstrated that chronic psychological stress alone decreased c-Fos expressions [ 61 ], while antipsychotic drug treatment increased c-Fos expressions in the PVN [ 63 ].…”

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

“…Actually, the c-Fos and related gene products belong to the transcription factors candidates that could create linkage between the acute cell surface receptor occupancy by APs and the gradual, long-lasting neural changes induced by their chronical treatment (Hiroi and Graybiel 1996). The long-lasting effect induced by APs repeated treatment can be monitored by the deltaFosB (ΔFosB), expression, a truncated splice variant of the FosB/ΔFosB gene (Kovacs 1998;Majercikova and Kiss 2015;Majercikova et al 2016;Kiss and Majercikova 2017;Osacka et al 2019). The functional significance of ΔFosB has been implicated in different experiments.…”