Non-drug treatments
1. Environmental Enrichment (EE):  It has been indicated alternations in neurotransmitters levels such as glutamate, serotonin, and decreased BDNF induced by chronic isolation were modified in EE (89). Social activity among rats exposed to a novel environment was higher than standard rats. These results proved the potentiality of nondrug protocols in improving mental deficits (97). Moreover, well-being in isolated patients is related to the quality of social support; consequently, any prescription to encourage being social and connected has been considered by the practitioner (98). EE, as a non-pharmacological treatment, has been applied in some investigation. Data have suggested that EE has enhanced social and cognitive deficits in isolated patients. Several researchers have exhibited the importance of positive and hopeful experiences in life to recover the brain from behavioral dysfunction (99).
Anti-depressant effects of EE have been demonstrated by investigations according to SI in rats (100). It has been shown that depression-related behavior and related abnormalities followed by long-term isolation, could be treated by EE. It can also perform as effective as fluoxetine; however, side effects associated with a pharmacological drug would not happen with EE treatment. Isolation-induced decrease in 5-HT level has been regulated through EE treatment, and the 5-HT level has increased in the hippocampus and prefrontal cortex (64). Finally, some investigations revealed that using an EE increases the rate of neurogenesis to maintain proliferation of dentate gyrus (DG) hippocampal cells in socially isolated mice, which results in maintaining social recognition memory and improving amnesic-like impairment (101).
In conclusion, EE plays a significant role in promoting neurogenesis in the hippocampus, impaired by social isolation.
2. Exercise:  Frequent physical exercise has been accepted among people to improve the physical and emotional conditions. By designing several studies on sports achievements, it has demonstrated that neurotransmitters’ functionality and brain plasticity have been modulated in socially isolated rodents (102). In several types of research, rats were forced to run on a treadmill,  which was a stressful condition. Results were disparate compared to voluntarily exercise, which resulted in regulating BDNF levels in isolated rats. Some other investigations have revealed that elective exercise cannot make any improvements in cognitive and social behavior impairments (103, 104). Eight weeks of running on a treadmill (30 min/day) have been shown to improve short-term and spatial working memory in SI rats (105). Regular treadmill exercise has improved isolation-induced depression-like behavior by regulating the hypothalamic-pituitary-adrenal (HPA) axis and this type of exercise has decreased stress hormones. Additionally, increased BDNF, NGF, serotonergic cells, and brain plasticity in the hippocampus have occurred after physical activity (22, 106).
Clinical research has revealed that walking  among adults has positively affected social experiences for people who have been isolated and lived alone. At the end of this research, adults have claimed an improvement in their feelings and are encouraged to start social relationships, to get to know new people, and finally, to leave isolating mood (107). As stated by the research on rats, it has indicated that the development of monoaminergic axons has been prevented during isolation periods in maternal separation (108). Eventually, voluntarily running exercise  has been found to stop emotional and social impairments by stimulating monoaminergic axons to start improvements again (109).
As claimed by more studies, pro-inflammatory and cytokine interleukin-1β (IL-1β) has been produced increasingly in the hippocampus during the adolescence period. Besides, Social isolation adversely affects the hippocampus neurogenesis. Adolescence is a critical period in hippocampus maturation, and any detrimental impact makes more impairment in adulthood (110, 111). These Researches have found that aerobic exercises  decreased stress induced by both adolescence and isolation in the hippocampus. Eventually, it has been demonstrated by some evidence that overexpression of IL-1β has been reversed by running and aerobic exercise during isolation housing in adolescence; while, supportive effects on neurogenesis occurred at the same time and resulted in developed recognition and social activity (111, 112). These findings explained how SI changed 5-hydroxytryptamine expression, and led to apoptosis in rats, which can account for cognition deficit and anxiety mood. Investigations have also designed an experiment to explore swimming  effects on socially isolated old rats (113).
Tryptophan hydroxylase positive cell, 5-hydroxytryptamine positive cells, and Bcl-2 (B-cell lymphoma 2) expression have increased while BAX (Bcl-2-associated X protein) and cytochrome c expres­sion were suppressed while swimming exercise. It was shown that swimming would lead to apopto­sis prevention, reduced anxiety, and enhancement in social and learning capability in rats (114).
As claimed via an earlier investigation, depression was seen after periods of SI, which impaired the glutamatergic system in the hippocampus and NMDA receptor co-agonist D-serine. It has revealed that endurance exercise  has attenuated adverse effects induced by isolation (115, 116). Amelioration of glutamate transmission has also decreased depressive behavior in rats. Therefore, exercising has been able to decline depression, social deficits, and cognition impairment induced by isolation experiences (117).
3. Music:  Music is well known as a way to express emotion and has effects on well-being feeling, regulating hormones, and neurotransmitters. Physicians have found  music therapy as a method to alleviate patients who had shown regression and weak sociability during housing isolation (118). Two types of patients, adults in the general ward of the hospital and children with leukemia in an isolated room, have experienced it as an enjoyable practice (119). They have claimed reduced fears, stress, and a motivated mood by listening to music. Besides, more verbalization, self-expression, and social relationships were reported. Beneficial impacts of listening to music have been performed by neurochemicals such as dopamine and oxytocin, which resulted in active talking and better communication (120). It has also enhanced health conditions in patients with Parkinson’s disease by increasing social benefit.
In conclusion, music has been considered a non-pharmacological treatment in isolated patients and SI (121).
4. Technology:  As mentioned earlier, the environment itself plays a critical role in brain function and development. Lack of social interaction, as an absence of social stimulation on the brain, may lead to lesser cognitive reserve, lower brain flexibility, and cognitive impairment (122). There are several investigations on using smartphones,  which have been used as a critical tool to connect humans and plays a crucial role in social capability and decreasing SI (123). Nowadays, social interaction has strictly wired into mobile phones via social platforms such as chat rooms, groups and channels, YouTube videos, and video-call applications like Skype. During the pandemic, when getting quarantine and staying at home was advised, social support has been provided mostly by social media throughout smartphones. People could join in social activities and feel like a helpful member of the community to reduce the detrimental effects of isolation (124). Social engagement  has shown to improve age-related cognitive deficits, dementia, and memory decline induced by SI. Moreover, a sense of belonging and connection with others in places like school has shown to be crucial for academic success (125).
During the COVID-19 pandemic, Attitudes towards social robots  have changed. Pieces of evidence have shown that people were encouraged to buy social robots more than ever. The emotional and behavioral features of those robots have made people feel less lonely and isolated; also, social support and reduced depressive-like mood were reported. A sense of happiness and having a better quality of life was seen through interactions with a robot, which was designed to behave socially interactive (126-128).
5. Farming:  Farming activities have been shown to regulate social functioning for those who are suffering from a mental disorder. Several investigations have revealed that farming activities moderated getting into the community and having a connection with people. Being with each other is essential for people with mental problems; therefore, drug treatments will not work when social bonds are weak. According to the current research, social farming has been useful for social interaction and fihjting isolation (129, 130).