Opening of T-type Ca2+ channels and activation of HCN channels contribute in stress adaptation in cold water immersion stress-subjected mice

Abstract

AimThe present study was designed to investigate the possible role of T-type Ca2+ channels and HCN channels in the development of stress adaptation in cold-water immersion stress-subjected mice. Material and methodsThe mice were subjected to cold-water immersion stress by placing them individually in a water tank (depth = 15.5 cm; temperature = 15 ± 2 °C) for 5 min. The mice were subjected to single episode of cold-water immersion stress for inducing acute stress; while for inducing stress adaptation, mice were subjected to repeated episodes of homotypic stressor (5 min) for 5 consecutive days. Animals were administered with ethosuximide (100 and 200 mg/kg, i.p.) and ivabradine (5 and 10 mg/kg, i.p.) before subjecting them to stress for five days. The stress-related behavioral alterations were assessed using the actophotometer, the hole board, the open field and the social interaction tests. The plasma corticosterone levels were quantified as a biochemical parameter of hypothalamic-pituitary-adrenal (HPA) axis activation. ResultsAcute stress altered the behavioral and biochemical parameters of the animals. However, repeated stress significantly restored the behavioral and biochemical alterations signifying the development of adaptation. Administration of ethosuximide and ivabradine abolished the restoration of behavioral and biochemical changes in the animals subjected to repeated stress. ConclusionThe ethosuximide and ivabradine mediated attenuation of stress adaptation demonstrates that the opening of T-type Ca2+ channels and activation of HCN channels are involved in inducing stress adaptation in repeated stress-subjected animals.