Brain and Anabolic steroids



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Anti Doping Denmark, Research seminar November 26 2013, Copenhagen Brain and Anabolic steroids Mathias Hallberg, Associate professor Department of Pharmaceutical Biosciences Division of Biological Research on Drug Dependence Headlines in media 22 year old bodybuilder killed her husband Han skulle bara ta en kort kvällspromenad och rasta hunden. Klockan var runt fem, hustrun stod med maten på spisen. Ingvar kom aldrig hem. En 22-årig kroppsbyggare fullproppad med anabola steroider stod i vägen. Doping made Fredrik crazy Fredrik, 15 år: normalbyggd och 70 kilo tung. Några år senare: uppumpad, testosteronstinn och 130 kilo. Jag blev kaxig och mallig, men också utåtriktad och glad. Jag mådde bra helt enkelt. Tio år senare kom smällen. Gladiator from TV ill-treated wife I tv var den 36-årige gladiatorn en hjälte. Men hemma åkte den tv-putsade gladiatormasken av. Nu sitter han fängslad för dopingbrott och grov Kvinnofridskränkning. 1

Desirable effects Increased muscle mass Increased muscular strength Increased energy ------ Increased self-esteem Aggression Anabolic steroids affects the brain Brain Euphoria Increased self-esteem Increased energy Increased motivation Aggression Risk of violent actions Irritability impulsivity Anxiety Depression Psychosiss 2

Common steroids on the market N N H Testosterone Nandrolone Stanozolol Methandrostenolone Tetrahydrogestrinone (THG) Physical effects of anabolic steroids Gynecomastia Baldness Striae Testicular atrophy Cardiovascular diseases 3

Steroid 1 Steroid 2 Steroid 3 HCG Week 1 10 mg/day Week 2 10 mg/day Week 3 10 mg/day Week 4 10 mg/day 200 mg Week 5 10 mg/day 200 mg Week 6 10 mg/day 200 mg Week 7 10 mg/day 200 mg 300 mg Week 8 10 mg/day 200 mg 300 mg Week 9 200 mg 300 mg Week 10 200 mg 300 mg Week 11 300 mg Week 12 300 mg Week 13 Week 14 Week 15 7500-10 000 IU 5000 7500 IU 5000 IU * Besides steroids and HCG, other substances that may minimize side-effects are recommended. Testosterone and the main metabolism 1 Testosterone Testosterone 2 H Dihydrotestosterone Dihydrotestosterone 1) 5α-reductase 2) aromatase H Estrogen Estradiol Receptors (targets) 4

Common substances Enzym inhibitors (inhibits the estrogen production) Anti-estrogens hcg β 2 -agonists (luftrörsvidgande) Growth hormone Stimulants Analgesics (opiates) Benzodiazepins -------------------------------------------------- Narcotics and poly-drug use is frequently reported Source: e.g Skårberg et al 2008 Subst Abuse Treat Prev Policy 3:24 Brain reward system GABA interneuron Endorphin Enkephalin Dopamine neuron Dopamine Dynorphin Nucleus accumbens VTA 5

Anabolic steroids increase the levels of β-endorphin in the drug reward system fmol/mg tissue Control AAS AAS 5mg/kg 15mg/kg Source: Johansson et al., 1997. Neurosci Res 27: 185-189 Anabolic steroids affect the dynorphin as well as dopamine receptors Source: Magnusson et al., 2009. Neuropeptides 43:105-111 Source: Kindlundh et al., 2001. Eur J Neurosci (13) 291-296 6

The effect of AAS on alcohol intake ethanol intake [g/kg/dag] 1.0 * 0.5 * AAS Control 0.0 vecka 1 vecka 2 vecka 3 Source: Johansson et al., 2000 Pharmacol Biochem Behavior 67: 271-279 AAS may induce a mild dependency (including both psychological and biological components) Self-administration of testosterone is blocked by dopamine receptor antagonists # Source: Wood RI (2008) Front neuroendocrinol. 29 (4):490-506 7

AAS as a gateway to drug dependence Harrison G Pope and co-workers: 1990: ne (0,5 %) of 197 heroin addicts has a history of AAS 1999: 21 (9,3 %) of 227 heroin addicts have a history of AAS 2003: 22 (25 %) of 88 heroin addicts have a history of AAS Anabolic androgenic steroids and criminality 8

AAS treated rats are more aggressive Reactivity score 4 2 *** 0 AAS AAS Kontroll Controls Source: Lindqvist et al 2002 Competition: AAS treated rats are more dominant Basline Competition Drinking time (sec) 350 300 250 200 150 100 50 0 * * AAS Control Source: Lindqvist et al 2002 Behav Brain Res, 133: 21-29 9

Pathways in aggression Source: Bitran et al 1996; Hallberg et al 2005; Hallberg et al 2000; Kindlundh et al 2003; LeGreves et al 1997 Conclusion Source: Nyberg and Hallberg, 2012 Int Rev Neurobiol 102:181-198 10

Thank you for listening! 11