Abstract
Rationale
Exercise participation remains low despite clear benefits. Rats engage in voluntary wheel running (VWR) that follows distinct phases of acquisition, during which VWR escalates, and maintenance, during which VWR remains stable. Understanding mechanisms driving acquisition and maintenance of VWR could lead to novel strategies to promote exercise. The two phases of VWR resemble those that occur during operant conditioning and, therefore, might involve similar neural substrates. The dorsomedial (DMS) dorsal striatum (DS) supports the acquisition of operant conditioning, whereas the dorsolateral striatum (DLS) supports its maintenance.
Objectives
Here we sought to characterize the roles of DS subregions in VWR. Females escalate VWR and operant conditioning faster than males. Thus, we also assessed for sex differences.
Methods
To determine the causal role of DS subregions in VWR, we pharmacologically inactivated the DMS or DLS of adult, male and female, Long-Evans rats during the two phases of VWR. The involvement of DA receptor 1 (D1)–expressing neurons in the DS was investigated by quantifying cfos mRNA within this neuronal population.
Results
We observed that, in males, the DMS and DLS are critical for VWR exclusively during acquisition and maintenance, respectively. In females, the DMS is also critical only during acquisition, but the DLS contributes to VWR during both VWR phases. DLS D1 neurons could be an important driver of VWR escalation during acquisition.
Conclusions
The acquisition and maintenance of VWR involve unique neural substrates in the DS that vary by sex. Results reveal targets for sex-specific strategies to promote exercise.
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Acknowledgements
The authors would like to thank Dr. Erik B. Oleson for proofreading the manuscript.
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Funding for these studies was provided by NIH R15MH114026 awarded to BNG.
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MKT and BNG designed the studies. MKT, JKPD, JJ, NAM, AAH, KB, KAA, NJ, RH, TJH, NB, and ECL contributed to data collection. MKT, JKPD, JJ, and BNG analyzed data. MKT and BNG wrote the manuscript. All authors edited paper drafts.
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Tanner, M.K., Davis, J.K.P., Jaime, J. et al. Duration- and sex-dependent neural circuit control of voluntary physical activity. Psychopharmacology 239, 3697–3709 (2022). https://doi.org/10.1007/s00213-022-06243-0
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DOI: https://doi.org/10.1007/s00213-022-06243-0