Abstract
We assessed the antidepressant-like effects of environmental enrichment (EE) and physical exercise (PE) compared with the selective serotonin reuptake inhibitor fluoxetine against the depression-related neurobehavioral alterations induced by postweaning social isolation (SI) in rats. After 1 month of SI, rats were submitted to PE (treadmill), EE, or fluoxetine (10 mg/kg), which were compared with naïve SI and group-housed rats. After 1 month, behavior was analyzed in the open field (OFT), the sucrose preference (SPT), and the forced swimming (FST) tests. Afterward, the hippocampal serotonin contents, its metabolite, and turnover were measured. SI induced a depression-related phenotype characterized by a marginal bodyweight gain, anxiety, anhedonia, behavioral despair, and alterations of serotonin metabolism. EE produced the widest and largest antidepressive-like effect, followed by PE and fluoxetine, which were almost equivalent. The treatments, however, affected differentially the neurobehavioral domains investigated. EE exerted its largest effect on anhedonia and was the only treatment inducing anxiolytic-like effects. Fluoxetine, in contrast, produced its largest effect on serotonin metabolism, followed by its anti-behavioral despair action. PE was a middle-ground treatment with broader behavioral outcomes than fluoxetine, but ineffective to reverse the serotonergic alterations induced by SI. The most responsive test to the treatments was the FST, followed closely by the SPT. Although OFT locomotion and body weight varied considerably between groups, they were barely responsive to PE and fluoxetine. From a translational standpoint, our data suggest that exercise and recreational activities may have broader health benefits than antidepressants to overcome confinement and the consequences of chronic stress.
Highlights
Chronic stress represents an important risk factor for many neuropsychiatric disorders, such as anxiety and affective disorders (Bao et al, 2008)
As groups were counterbalanced according to body weight, no significant differences were observed at the baseline level (PND 30) (Figure 1B)
Our social isolation (SI) rats maintained a consistent, yet non-significant increase of ~4% in body weight compared to standard housing (SH) animals (Figure 1B)
Summary
Chronic stress represents an important risk factor for many neuropsychiatric disorders, such as anxiety and affective disorders (Bao et al, 2008). Concerning 5-HT neurotransmission, several studies showed decreased basal contents (Jaffe et al, 1993), release deficits in response to further stressor exposures (Muchimapura et al, 2002), changes in the transmitter turnover (Brenes and Fornaguera, 2009), and alterations in receptor binding or responsiveness (Wright et al, 1991; Muchimapura et al, 2003; Marsden et al, 2011). These findings evidence a pivotal role of the 5-HTergic system in the control of SIinduced effects
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