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

Author:

Kawashima Hiroki1,Aono Yuri2,Shimba Shigeki3,Waddington John L.4,Saigusa Tadashi12ORCID

Affiliation:

1. Oral Molecular Pharmacology Nihon University Graduate School of Dentistry at Matsudo Matsudo Chiba Japan

2. Department of Pharmacology Nihon University School of Dentistry at Matsudo Matsudo Chiba Japan

3. Laboratory of Health Science Nihon University School of Pharmacy Funabashi Chiba Japan

4. School of Pharmacy and Biomolecular Sciences RCSI University of Medicine and Health Sciences Dublin Ireland

Abstract

AbstractNandrolone, 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.

Funder

Japan Society for the Promotion of Science

Nihon University

Publisher

Wiley

Subject

Cellular and Molecular Neuroscience

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