The ability of the biological system to cope stressful condition plays a crucial role in the body [
33]. Stress activates hypothalamus - pituitary - adrenal axis (HPA) axis and influences several neurological function at both central and peripheral level. Any kind of stress influences brain functions by causing long term changes in the multiple neural systems [
34,
35]. Restraint stress has been reported to influence motor activity, caused pain perception [
37] anxiety like behavior [
36], and depression-like behaviors [
38] in the animals. In the present study, 6-hr restraint stress significantly caused anxiety like behavior, impaired motor activity and antinocieption, indicating stress induced neurobehavioral alterations. Stress has already been reported to alter neurobehavioral in both acute as well as chronic stress [
38]. Marked behavioral changes might be due to alteration in the brain regions controlling motor activity and anxiety like behavior. Impaired motor activity could be due to stress induced depression. Further, St. John's Wort treatment for five days significantly improved behavior alterations, suggesting its neuroprotective effect against stressful conditions. Antidepressants have been reported to alleviate stress and stress related effects [
39,
40]. Recently, neuroprotective effects of antidepressants have been reported [
45]. However, scientific mechanistic explanations of their clinical efficacy for treatment of depression are not been fully understood so far. Present study further suggests its therapeutic potential against these stress related altered behavioral states. Further, five days St. John's Wort treatment did not influence significantly antinociceptive effect. This might be due to its own analgesic effect, antianxiety and improved locomotor activity. In the present study, St. John's Wort treatment significantly produced analgesic effect. Antidepressant drugs have been widely used for many years to treat pain and related states, despite unclear rationale of their clinical use [
45]. Their mechanisms of action (noradrenergic, serotonergic, opioids), focusing on central and peripheral analgesic actions are still not clear.
Oxidative stress causes cellular damage and accelerates neuro-degeneration by inducing the reactive oxygen species (ROS) that oxidize vital cellular components such as lipids, proteins and DNA [
41,
42]. In the present study, 6-hr immobilized stress caused significantly oxidative damage as indicated by raise in lipid peroxidation, nitrite concentration and depletes reduced GSH and catalase activity. Tsuboi et al reported an increased oxidative damage and weak antioxidant defense events are implicated in major depression [
43]. In the present study, St. John's Wort treatment significantly attenuated lipid peroxidation, nitrite concentration and partially restored GSH and catalase activity suggesting its antioxidant like effect. Supporting to our study, clinical trial also indicates that raised level of MDA in patients with affective disorders [
44]. Besides, other antidepressant such as fluoxetine has also been reported to reduce the maloanodialdehyde level in restraint animals [
45]. Antidepressants drugs have also been reported to elevated antioxidant enzyme defense system particularly superoxide enzyme and catalase activity [
46]. These antioxidant enzymes raised the level of oxidative defense against stress.