Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction

Robison, Lisa S.; Swenson, Sabrina; Hamilton, John; Thanos, Panayotis K.

doi:10.1249/mss.0000000000001627

Cited by 64 publications

(73 citation statements)

References 48 publications

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“…Indeed, D 2 R protein density was subtly increased by wheel running in the DMS, AcC, and AcS compared to sedentary mice (see Figure 2(f)), despite overall trends towards greater density in other striatal subregions that failed to reach statistical significance. This finding is consistent with several reports of mildly increased D 2 R mRNA levels, protein density, and ligand binding affinity in the striatum following periods of exercise [65][66][67][68][69][70][71]. Finally, physical activity status had no impact on the density of D 1 R protein (see Figure 2(i)), which has also been reported in previous literature [70,71].…”

Section: Discussionsupporting

confidence: 92%

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System

2020

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Adenosine acts as a key regulator of striatum activity, in part, through the antagonistic modulation of dopamine activity. Exercise can increase adenosine activity in the brain, which may impair dopaminergic functions in the striatum. Therefore, long-term repeated bouts of exercise may subsequently generate plasticity in striatal adenosine systems in a manner that promotes dopaminergic activity. This study investigated the effects of long-term voluntary wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor protein expression in adult mouse dorsal and ventral striatum structures using immunohistochemistry. In addition, equilibrative nucleoside transporter 1 (ENT1) protein expression was examined after wheel running, as ENT1 regulates the bidirectional flux of adenosine between intra- and extracellular space. The results suggest that eight weeks of running wheel access spared age-related increases of A1R and A2AR protein concentrations across the dorsal and ventral striatal structures. Wheel running mildly reduced ENT1 protein levels in ventral striatum subregions. Moreover, wheel running mildly increased D2R protein density within striatal subregions in the dorsal medial striatum, nucleus accumbens core, and the nucleus accumbens shell. However, D1R protein expression in the striatum was unchanged by wheel running. These data suggest that exercise promotes adaptations to striatal adenosine systems. Exercise-reduced A1R and A2AR and exercise-increased D2R protein levels may contribute to improved dopaminergic signaling in the striatum. These findings may have implications for cognitive and behavioral processes, as well as motor and psychiatric diseases that involve the striatum.

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Section: Discussionsupporting

confidence: 92%

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System

2020

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“…Exercise increased serum dopamine levels and adrenalectomy prevented this effect and the control of serum TNF levels. Similar recent studies showed that moderate exercise can induce dopamine, which contributes to the mesolimbic reward pathway during exercise (Mitchell et al, 2018; Robison et al, 2018; Rosso et al, 2018), enhances cognition by activating D1-dopaminergic receptors (McMorris, 2016a,b), protects dopaminergic neurons against inflammation-induced degeneration (Wu et al, 2011), decreases oxidative stress and inflammation, and restores renal dopamine D1 receptors function in elderly rats (Asghar et al, 2007). Our results show that dopamine inhibited LPS-induced TNF production of primary culture of splenocytes in a concentration dependent manner.…”

Section: Discussionmentioning

confidence: 64%

Exercise activates vagal induction of dopamine and attenuates systemic inflammation

Shimojo

Joseph

Shah

et al. 2019

Brain, Behavior, and Immunity

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Physical exercise is one of the most important factors improving quality of life, but it is not feasible for patients with morbidity or limited mobility. Most previous studies focused on high-intensity or long-term exercise that causes metabolic stress or physiological adaption, respectively. Here, we studied how moderate-intensity swimming affects systemic inflammation in 6–8 week old C57BL/6J male mice during endotoxemia. One-hour swimming prevented hypokalemia, hypocalcemia, attenuated serum levels of inflammatory cytokines, increased anti-inflammatory cytokines but affected neither IL6 nor glycemia before or after the endotoxic challenge. Exercise attenuated serum TNF levels by inhibiting its production in the spleen through a mechanism mediated by the subdiaphragmatic vagus nerve but independent of the splenic nerve. Exercise increased serum levels of dopamine, and adrenalectomy prevented the potential of exercise to induce dopamine and to attenuate serum TNF levels. Dopaminergic agonist type-1, fenoldopam, inhibited TNF production in splenocytes. Conversely, dopaminergic antagonist type-1, butaclamol, attenuated exercise control of serum TNF levels. These results suggest that vagal induction of dopamine may contribute to the anti-inflammatory potential of physical exercise.

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“…Results from this and previous studies suggest that exercise may affect one or both of these brain regions that is/are common to the variety of relapse pathways, since exercise has been shown to alter reinstatement due to each of these priming stimuli [52–54, 78]. Future research should examine the possible mechanisms involved in driving these behavioral changes, including alterations to the mesolimbic dopamine pathway seen following exercise [55, 56]. Alternatively, it is also possible that exercise facilitated the forgetting of the cocaine-paired chamber, possibly due to memory clearance/degradation resulting from exercise-induced increases hippocampal neurogenesis [90, 91].…”

Section: Discussionmentioning

confidence: 90%

“…Previous rodent studies have confirmed exercise’s ability to reduce the acquisition and escalation of drug preference and self-administration [45–50], increase the breakpoint for operant responding for psychostimulants [51], and attenuate other types of primed reinstatement (drug-primed and cue-induced) [52–54]. These exercise-induced changes in drug-seeking behavior may be linked to alterations in the mesolimbic dopamine pathway [55, 56], which mediates the rewarding/reinforcing properties of drugs of abuse [57, 58]. Very few studies, however, have investigated the ability of exercise to prevent stress-induced relapse specifically.…”

Section: Introductionmentioning

confidence: 99%

Chronic forced exercise inhibits stress-induced reinstatement of cocaine conditioned place preference

Robison¹,

Alessi

Thanos³

2018

Behavioural Brain Research

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Stress increases the likelihood of cocaine relapse in humans and animals, even following a prolonged extinction/abstinence period. Exercise has previously been shown to reduce stress and decrease the likelihood of drug dependence, while also reducing cravings in humans and inhibiting relapse behaviors due to other risk factors in rodents. The present study evaluated the efficacy of exercise to reduce stress-induced relapse to cocaine in a rodent model. Young adult female Sprague Dawley rats were tested for cocaine conditioned place preference (CPP), then split into sedentary or exercise (six weeks of one-hour daily treadmill running, five days per week) groups. Following cocaine CPP, rats were tested for extinction behavior, and then tested for stress-primed reinstatement (15 min immobilization) following the six-week intervention period. Exercise inhibited stress-induced reinstatement of cocaine CPP despite increasing serum corticosterone levels following 15 min of immobilization, suggesting that chronic aerobic exercise intervention may result in adaptations of stress pathways. These findings suggest that exercise may help prevent stress-induced drug relapse, adding to a growing body of evidence supporting the utility of exercise to combat substance abuse.

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Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction

Abstract: These findings support the hypothesis that aerobic exercise results in changes in the mesolimbic pathway that could mediate exercise-induced attenuation of drug-seeking behavior.

Cited by 64 publications

References 48 publications

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System

Exercise activates vagal induction of dopamine and attenuates systemic inflammation

Chronic forced exercise inhibits stress-induced reinstatement of cocaine conditioned place preference

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