Effects of anabolic androgenic steroids on the development and expression of running wheel activity and circadian rhythms in male rats.
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.
McGinnis
Marilyn Y
MY
Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States.
Lumia
Augustus R
AR
Tetel
Marc J
MJ
Molenda-Figueira
Heather A
HA
Possidente
Bernard
B
D045930:Anabolic Agents / Q000008:administration & dosage* / Q000097:blood; D000728:Androgens / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051548:Histone Acetyltransferases / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2 / Q000378:metabolism; D051381:Rats; D012420:Running; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D045930:Anabolic Agents; D000728:Androgens; D051958:Nuclear Receptor Coactivator 2; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1
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