Effects of anabolic androgenic steroids on the development and expression of running wheel activity and circadian rhythms in male rats
Open accessAbstract
In humans, anabolic androgenic steroid (AAS) use has been associated with hyperactivity and disruption of circadian rhythmicity. We used an animal model to determine the impact of AAS on the development and expression of circadian function. Beginning on day 68 gonadally intact male rats received testosterone, nandrolone, or stanozolol via constant release pellets for 60 days; gonadally intact controls received vehicle pellets. Wheel running was recorded in a 12:12 LD cycle and constant dim red light (RR) before and after AAS implants. Post-AAS implant, circadian activity phase, period and mean level of wheel running wheel activity were compared to baseline measures. Post-AAS phase response to a light pulse at circadian time 15 h was also tested. To determine if AAS differentially affects steroid receptor coactivator (SRC) expression we measured SRC-1 and SRC-2 protein in brain. Running wheel activity was significantly elevated by testosterone, significantly depressed by nandrolone, and unaffected by stanozolol. None of the AAS altered measures of circadian rhythmicity or phase response. While SRC-1 was unaffected by AAS exposure, SRC-2 was decreased by testosterone in the hypothalamus. Activity levels, phase of peak activity and circadian period all changed over the course of development from puberty to adulthood. Development of activity was clearly modified by AAS exposure as testosterone significantly elevated activity levels and nandrolone significantly suppressed activity relative to controls. Thus, AAS exposure differentially affects both the magnitude and direction of developmental changes in activity levels depending in part on the chemical composition of the AAS.
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Both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development.
“This meant that, overall, both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development, similar to human adolescents (Figure 2C-D, [66-67, 75, 114, 185]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
The pubertal shift in rest/activity rhythms in rodents is similar to that in human adolescents.
“This meant that, overall, both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development, similar to human adolescents (Figure 2C-D, [66-67, 75, 114, 185]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
Two studies in laboratory rats also revealed a change in free-running period around the time of puberty.
“Two studies in laboratory rats also revealed a change in free-running period around the time of puberty [66, 114].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
The changes observed in the free-running period of male rats during puberty in our study are opposite of what was found in an earlier study by a collaborator.
“To complicate matters, the changes that we observed in the free-running period of male rats during puberty in our study are actually the opposite of what was found in an earlier study by a collaborator [114].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
In both rat studies, the free-running period of male and female rats was closest to 24 h during the youngest developmental time point, immediately after placement into constant conditions.
“In both of the rat studies [66, 114], the free-running period of the male and female rats was closest to 24 h during the youngest developmental time point, immediately after placement into constant conditions.”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
Circadian phase is more delayed during puberty than adulthood in rats and degus, as it is in humans and macaques.
“However, the observation was clearly replicated that circadian phase is more delayed during puberty than adulthood [75, 114] as it is in humans and macaques [60, 160].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [114]
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SLEEP-WAKE RHYTHMS AND COGNITION
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- Authors
- McGinnis, M. Y., Lumia, A. R., Tetel, M. J., Molenda-Figueira, H. A., & Possidente, B.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Wellesley College (US)
- Skidmore College (US)
- Corresponding author
- Possidente, Bernard
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 92
- Issue
- 5
- Pages
- 1010-1018
- ISSN
- 0031-9384 (ISSN-L)
- PMC
- PMC4476530
- OpenAlex
- W2107584519
- Cited by
- 58
- References
- 66
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA10886, R01DA010886)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK61935, R55DK061935, R01DK061935)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- anabolic steroids, testosterone, nandrolone, stanozolol, wheel running, circadian rhythm, steroid receptor coactivators, SRC-1, SRC-2, hypothalamus, puberty, circadian period, phase response, light pulses, male rats
- MeSH terms
- Androgens, Animals, Animals, Newborn, Behavior, Animal, Body Weight, Circadian Rhythm, Male, Motor Activity, Running, Time Factors, Transcription Factors, Gene Expression Regulation, Developmental, Anabolic Agents, Rats, Histone Acetyltransferases, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 1
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