TRPA1 MUTATION AFFECTS BEHAVIORAL AND ENDOCRINOLGICAL RESPONSE TO CHRONIC VARIABLE MILD STRESS

01/29/2020

Viktória Kormos¹, József Farkas², Tamás Gaszner², Angéla Kecskés¹, Zsuzsanna Helyes¹, Erika Pintér¹, Balázs Gaszner²

¹ Dept. of Pharmacology and Pharmacotherapy, 2Dept. of Anatomy University of Pécs, Pécs

Transient receptor potential cation channel subfamily A member 1 (TRPA1) is involved in nociception, thermoregulation and inflammatory responses. As the role of TRPA1 receptors in a complex adaptation to environmental challenges was not studied yet, we aimed at investigating the chronic variable mild stress (CVMS) adaptation response of the TRPA1 knockout (KO) mice. We hypothesized that KO mice will show altered response to CVMS. TRPA1 KO mice and wildtype (WT) counterparts were subjected to CVMS for three weeks vs. controls. Behavioral assessment was performed in marble burying (MBT), tail suspension (TST), forced swim (FST) and sucrose preference (SPT) tests. CVMS exposure increased anxiety levels in MBT. A similar tendency was observed in TST for depression level. In FST, control TRPA1 KO mice exerted higher depression level which did not increase upon CVMS, in contrast to that of WT mice. CVMS increased the anhedonia level in SPT in both genotypes that was in line with blood corticosterone level. Control TRPA1 KO mice showed reduced weight gain compared to WT animals. CVMS attenuated bodyweight gain in both genotypes. Upon CVMS, TRPA1 KO mice had larger relative adrenal weights but, the relative thymus weight was reduced by CVMS in WT mice only. In summary, TRPA1 knockout mice show altered response to CVMS in depression and anxiety tests. Thymus- adrenal- and bodyweight data in TRPA1 KO mice upon CVMS exposure suggest the long-term change of hypothalamus-pituitary-adrenal axis activity. In our ongoing experiments we study the underlying central mechanisms. Support: KA-2019-12, KTIA-NAP-13-1-2013-0022, GINOP-2.3.2-15-2016-00050, GINOP-2.3.2-15-2016-00048, EFOP-3.6.2-16-2017-00008.