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Adolescence as a critical period for nandrolone-induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats

journal contribution
posted on 2023-03-01, 09:12 authored by Hiroki Kawashima, Yuri Aono, Shigeki Shimba, John WaddingtonJohn Waddington, Tadashi Saigusa

Nandrolone, an anabolic androgenic steroid, is included in the prohibited list of the World Anti-Doping Agency. Drugs of abuse activate brain dopamine neurons and nandrolone has been suspected of inducing dependence. Accordingly, possible critical periods for the effects of nandrolone on muscular strength and dopaminergic activity have been investigated, including the effects of chronically administered nandrolone alone and on morphine-induced increases in dopamine efflux in the nucleus accumbens. Six- or 10-week-old male Sprague-Dawley rats were used. Treatment with nandrolone was initiated in adolescent (6-week-old) and young adult (10-week-old) rats. Nandrolone (5.0 mg/kg s.c.) or sesame oil vehicle was given once daily, on six consecutive days per week, for 3 weeks and then once per day for 4 consecutive days. Nandrolone enhanced the developmental increase in grip strength of 6- but not 10-week-old rats, without altering the developmental increase in body weight of either age group. Using in vivo microdialysis in freely moving 6-week-old rats given nandrolone for 4 weeks, basal accumbal dopamine efflux was unaltered, while the increase in dopamine efflux induced by acute administration of morphine (1.0 mg/kg s.c.) was reduced. The present study provides in vivo evidence that adolescence constitutes a critical period during which repeated administration of nandrolone enhances increases in muscular strength without influencing increases in body weight. Though repeated administration of nandrolone during this period of adolescence did not stimulate in vivo mesolimbic dopaminergic activity, it disrupted stimulation by an opioid, the drug class that is most commonly coabused with nandrolone. 

Funding

JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (#21K10124; #21K10081) from The Japan Society for the Promotion of Science

Nihon University President's Grant for Specified Interdisciplinary Research

Suzuki Fund

Research Institute of Oral Science, Nihon University School of Dentistry at Matsudo

Nakatomi Foundation, Japan

History

Comments

This is the peer reviewed version of the following article:, Kawashima H, Aono Y, Shimba S, Waddington JL, Saigusa T. Adolescence as a critical period for nandrolone-induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats. Synapse. 2023, which has been published in final form at https://doi.org/10.1002/syn.22262 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Published Citation

Kawashima H, Aono Y, Shimba S, Waddington JL, Saigusa T. Adolescence as a critical period for nandrolone-induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats. Synapse. 2023;77(3):e22262.

Publication Date

13 January 2023

PubMed ID

36637118

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Publisher

Wiley

Version

  • Accepted Version (Postprint)