Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum

Abstract

Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress). Impaired escape behavior is a result of stress-sensitized serotonin (5-HT) neuron activity in the dorsal raphe (DRN) and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA) levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS) and lateral (DLS) dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.

Bidirectional longitudinal relationship between leisure-time physical activity and psychotropic medication usage: A register linked follow-up study

“…For instance, physical activity has been found to normalize reduced levels of brain-derived neurotrophic factor and therefore has neuro-protective or even neurotrophic effects (Szuhany et al, 2015). Animal studies have found physical activity-induced changes in the levels of different neurotransmitters such as dopamine (Clark et al, 2015), serotonin (Otsuka et al, 2016), glutamate (Real et al, 2010), and acetylcholine (Uchida et al, 2006), which relate to mood and beneficial effects on stress reactivity (e.g., the hypothalamuspituitary-adrenal axis). Potential psychosocial mechanisms include Table 3 Odds ratios (95% CI) and proportions (%) for physical inactivity (phase 2) by any psychotropic medication (phases 1-2).…”

Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling

“…Transcriptional changes in the striatum, a major component of the mesolimbic dopaminergic reward pathway, were examined in order to provide insight into the mechanisms underlying reduced ethanol preference. Wheel running in rodents has been shown to induce a myriad of behavioral responses related to tests of stress, anxiety, and depression (Adlard and Cotman, 2004; Brené et al, 2007; Clark et al, 2015; Dishman et al, 2006; Greenwood et al, 2011, 2013; Hare et al, 2014; Lapmanee et al, 2013; Loughridge et al, 2013; Mika et al, 2015; Sciolino et al, 2015; Sierakowiak et al, 2014). Furthermore, previous studies have demonstrated wheel running was sufficient to reduce voluntary intake of amphetamine (Kanarek et al, 1995), cocaine (Cosgrove et al, 2002; Smith et al, 2011), as well as nicotine-seeking during extinction (Sanchez et al, 2013; Smith and Lynch, 2011).…”

Altered monoamine levels in the dorsal striatum of the rat are associated with alterations in behavioural selection and motivation following peripheral nerve injury and acute stress

“…Neurons in the substantia nigra pars compacta (SNc) code for the intensity of noxious stimulus and enhancing or reducing dopaminergic activity in the dorsal striatum is associated with analgesia or enhanced pain, respectively. The pain in conditions such as Parkinson's disease and Complex Regional Pain Syndrome is associated with abnormal striatal function (Becerra et al., ; Campus et al., ; Carlson, Fitzgerald, Keller, & Glick, ; Clark et al., ; Geha et al., ; Goodman et al., ).…”