Akademik Veri Yönetim Sistemi
36th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Barcelona, İspanya, 7 - 10 Ekim 2023, cilt.2, ss.65
G. Çelebi1, S.S. Gocmez1, G. Bugutekin1,
Tijen Utkan1,2
1Kocaeli
University, Faculty of Medicine, Department of Pharmacology, Kocaeli, Turkey
2 Kocaeli
University, Experimental Medical Research and Application Centre, Kocaeli,
Turkey
Background: Social isolation
during early-life is one of the major sources of chronic stress and it may
contribute to the occurrence of mental disorders such as anxiety, depression
and schizophrenia. Moreover, many studies suggested that chronic psychological
stress is an important risk factor for cardiovascular diseases such as hypertension
and vascular endothelial dysfunction. There is evidence that social isolation,
which is used as one of the chronic stress sources in experimental animals,
causes various emotional and cardiovascular changes in rodents. Pioglitazone, PPARɤ
agonist, used as antidiabetic drug and has also vasculoprotective and
neuroprotective effects shown in different animal models such as hypertension,
hyperlipidemia and obesity. However, whether pioglitazone has therapeutic
effects on anxiety and vascular endothelial dysfunction are still unknown. The present study aimed to investigate the
effects of pioglitazone on anxiety-like behavior and vascular changes in rats
exposed to chronic social isolation stress.
Methods: Post-weaned (21 days
old) Wistar albino male rats were divided into 4 groups (n=12/group): Control,
Control+Pioglitazone, Social isolation (SI), Social isolation (SI)+Pioglitazone.
The housing conditions of the control groups were not changed and they were allowed
to house as 3 rats/cage. Rats in the social isolation group were housed in
individual cages to perform the 8-week isolation protocol. Pioglitazone (30
mg/kg/day p.o) was applied in the last 16 days of the social isolation
protocol. At the end of the 8-week isolation period, the elevated plus maze
test was performed to assess anxiety-like behaviors. The time that the animal
took to move from to the enclosed arm either one of the open arms was used as
an index of anxiety-like behavior in this test. The behavioral tests were
recorded with the support of video-tracking software (EthoVision XT10; Noldus
Information Technology, Wageningen, the Netherlands). After behavioral test,
rats in all groups were sacrified with anesthesia. The thoracic aorta samples
were collected for the assessment of vascular functions with isolated organ
bath experiments. To analyze the vascular reactivity, the endothelium-dependent
and -independent vasorelaxant responses of thoracic aorta were investigated by
carbachol (10-8-10-5 M) and sodium nitroprusside (10-8-10-4
M) after preincubation with phenylephrine (10-5 M) in organ
chambers.
Results: The total time to
spent in open arms in the elevated plus maze test was significantly decreased
in SI group, indicating that anxiety-like behavior, whereas increased in
SI+pioglitazone group (p<0.05). In SI group, endothelium-dependent
relaxation to carbachol was significantly decreased compared to control
(p<0.05), whereas pioglitazone treatment during SI period significantly
reversed this response to the controls. Endothelium-independent relaxations to
sodium nitroprusside was found similar in all groups. One way ANOVA following
post hoc Tukey test were used for the statistical analysis and p<0.05 was considered significant.
Conclusion: These findings
indicate that the chronic pioglitazone treatment may prevent vascular endothelial
dysfunction associated with anxiety-like behavior in chronic stress model of social
isolation in rats. However, further studies are needed to explore the
mechanisms of pioglitazone in this animal model.
Acknowledgement: This
work was supported by Scientific Research Projects of Kocaeli University,
Turkey (TDK-2022-3192).
Key words: social isolation,
pioglitazone, anxiety-like behavior, chronic stress, vascular function